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Viruses

Czub, M., H. Weingartl, S. Czub, R. He, and J. Cao (2005). Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 23(17-18): 2273-2279. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) remains a threat to cause epidemics as evidenced by recent sporadic cases in China. In this communication, we evaluated the efficacy and safety of two SARS vaccine candidates based on the recombinant modified vaccinia Ankara (MVA) expressing SARS-CoV spike or nucleocapsid proteins in ferrets. No clinical signs were observed in all the ferrets challenged with SARS-CoV. On the other hand, vaccination did not prevent SARS-CoV infection in ferrets. In contrast, immunized ferrets (particularly those immunized with rMVA-spike) exhibited significantly stronger inflammatory responses and focal necrosis in liver tissue after SARS-CoV challenge than control animals. Thus, our data suggest that enhanced hepatitis is linked to vaccination with rMVA expressing SARS-CoV antigens.
Descriptors: ferrets, sars virus, viral vaccines, viral antigens, hepatitis, immunology, RNA, viral analysis, severe acute respiratory syndrome.

Fan, J., X. Liang, M.S. Horton, H.C. Perry, M.P. Citron, G.J. Heidecker, T.M. Fu, J. Joyce, C.T. Przysiecki, P.M. Keller, V.M. Garsky, R. Ionescu, Y. Rippeon, L. Shi, M.A. Chastain, J.H. Condra, M.E. Davies, J. Liao, E.A. Emini, and J.W. Shiver (2004). Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine 22(23-24): 2993-3003. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: A universal influenza virus vaccine that does not require frequent updates and/or annual immunizations will offer significant advantages over current seasonal flu vaccines. The highly conserved influenza virus A M2 membrane protein has been previously suggested as a potential antigen target for such a vaccine. Here, we report systematic evaluation of M2 peptide conjugate vaccines (synthetic peptides of M2 extracellular domain conjugated to keyhole limpet hemocyanin (KLH) or Neisseria meningitidis outer membrane protein complex (OMPC)) in mice, ferrets, and rhesus monkeys. The conjugate vaccines were highly immunogenic in all species tested and were able to confer both protection against lethal challenge of either H1N1 or H3N1 virus in mice and reduce viral shedding in the lower respiratory tracts of mice and ferrets. The protection against lethal challenge in mice could also be achieved by passive transfer of monkey sera containing high M2 antibody titers. In addition, we showed that M2 antisera were cross reactive with M2 peptides derived from a wide range of human influenza A strains, but they failed to react with M2 peptides of the pathogenic H5N1 virus (A/Hong Kong/97). The data presented here will permit better understanding of the potential of an M2-based vaccine approach.
Descriptors: ferrets, mice, rhesus, influenza A virus, influenza vaccines, orthomyxoviridae infections, antibodies, lung virology, Macaca mulatta, inbred Balb C mice, nasal mucosa virology, neisseria meningitidis, conjugate vaccines, virus replication.

Govorkova, E.A., J.E. Rehg, S. Krauss, H.L. Yen, Y. Guan, M. Peiris, T.D. Nguyen, T.H. Hanh, P. Puthavathana, H.T. Long, C. Buranathai, W. Lim, R.G. Webster, and E. Hoffman (2006). Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004. Journal of Virology 80(12): 6195. ISSN: 0022-538X.
NAL Call Number: QR360.J6
Descriptors: ferrets, influenza virus, H5N1, humans, poultry, leathality.

Govorkova, E.A., J.E. Rehg, S. Krauss, H.L. Yen, Y. Guan, M. Peiris, T.D. Nguyen, T.H. Hanh, P. Puthavathana, H.T. Long, C. Buranathai, W. Lim, R.G. Webster, and E. Hoffmann (2005). Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. Journal of Virology 79(4): 2191-2198. ISSN: 0022-538X.
NAL Call Number: QR360.J6
Abstract: The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.
Descriptors: ferrets, influenza virus, genetics, mortality, avian pathogenicity, orthomyxoviridae pathogenicity, influenza pathology, influenza A virus, avian classification, poultry diseases.

Govorkova, E.A., R.J. Webby, J. Humberd, J.P. Seiler, and R.G. Webster (2006). Immunization with reverse-genetics-produced H5N1 influenza vaccine protects ferrets against homologous and heterologous challenge. Journal of Infectious Diseases 194(2): 159-167. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Abstract: BACKGROUND: Multiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine. METHODS: Ferrets were immunized with inactivated whole-virus vaccine produced by reverse genetics with the hemagglutinin (HA) and neuraminidase genes of A/HK/213/03 virus. Ferrets received a single dose of vaccine (7 or 15 microg of HA) with aluminum hydroxide adjuvant or 2 doses (7 microg of HA each) without adjuvant and were challenged with 10(6) 50% egg infectious doses of A/HK/213/03, A/HK/156/97, or A/Vietnam/1203/04 virus. RESULTS: One or 2 doses of vaccine induced a protective antibody response to the vaccine strain. All immunization regimens completely protected ferrets from challenge with homologous wild-type A/HK/213/03 virus: no clinical signs of infection were observed, virus replication was significantly reduced (P<.05) and was restricted to the upper respiratory tract, and spread of virus to the brain was prevented. Importantly, all vaccinated ferrets were protected against lethal challenge with the highly pathogenic strain A/Vietnam/1203/04. The 2-dose schedule induced higher levels of antibodies that were cross-reactive to antigenically distinct H5N1 viruses. CONCLUSIONS: H5N1 vaccines may stimulate an immune response that is more cross-protective than what might be predicted by in vitro assays and, thus, hold potential for being stockpiled as "initial" pandemic vaccines.
Descriptors: ferrets, immunology, virology, influenza A virus, H5N1, vaccines, orthomyxoviridae infections.
Notes: Comment In: J Infect Dis. 2006 Jul 15;194(2):143-5.

Hampson, A.W. (2006). Ferrets and the challenges of H5N1 vaccine formulation. Journal of Infectious Diseases 194(2): 143-145. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Descriptors: ferrets, immunology, virology, influenza A virus, H5N1, influenza vaccines, biosynthesis, vaccines, orthomyxoviridae infections.
Notes: Comment On: J Infect Dis. 2006 Jul 15;194(2):159-67.

Herlocher, M.L., R. Truscon, S. Elias, H.L. Yen, N.A. Roberts, S.E. Ohmit, and A.S. Monto (2004). Influenza viruses resistant to the antiviral drug oseltamivir: Transmission studies in ferrets. Journal of Infectious Disease 190(9): 1627-1630. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Abstract: Three type A influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. Previously, in the ferret model, an R292K mutant of a type A (H3N2) virus was not transmitted under conditions in which the wild-type virus was transmitted. This model was used to investigate whether the E119V mutant of a type A (H3N2) virus and the H274Y mutant of a type A (H1N1) virus would be transmitted under similar circumstances. Both mutant viruses were transmitted, although the H274Y mutant required a 100-fold-higher dose for infection of donor ferrets and was transmitted more slowly than was the wild type. Both the mutant and the wild-type viruses retained their genotypic characteristics.
Descriptors: ferrets, acetamides, antiviral agents, viral drug resistance, influenza A virus, orthomyxoviridae infections transmission, virology, disease models.

Herlocher, M.L., R. Truscon, R. Fenton, A. Klimov, S. Elias, S.E. Ohmit, and A.S. Monto (2003). Assessment of development of resistance to antivirals in the ferret model of influenza virus infection. Journal of Infectious Diseases 188(9): 1355-1361. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Abstract: We attempted to develop in vivo resistance of influenza virus to amantadine and to zanamivir, by use of the ferret model of influenza virus infection. Resistance of influenza virus A/LosAngeles/1/87 (H3N2) to amantadine was generated within 6 days, during a single course of treatment, and mutations in the M2 gene that are characteristic of human infections were observed. In contrast, during an identical single course of treatment with zanamivir, no evidence of reduced susceptibility was demonstrated. Pooled virus shed by zanamivir-treated ferrets was used to infect another group of ferrets. Twenty virus clones grew in plaque assays containing zanamivir, indicating possible reduced susceptibility; however, none exhibited reduced susceptibility to zanamivir in neuraminidase (NA) inhibition assays. Sequencing of the NA gene of these clones revealed only a noncoding nucleotide mutation at position 685. Sequencing of the hemagglutinin gene revealed mutations at positions 53, 106, 138, 145, 166, and 186. Similar to the situation in humans, amantadine use in ferrets rapidly produces antiviral resistance, but zanamivir use does not, although nucleotide changes were observed.
Descriptors: ferrets, amantadine, antiviral agents, influenza A virus, orthomyxoviridae infections, sialic acids, animal disease models, drug resistance, viral genetics, guanidines, hemagglutination inhibition tests, viral chemistry, RNA, reverse transcriptase polymerase chain reaction, DNA sequence analysis.

Huber, V.C. and J.A. McCullers (2006). Live attenuated influenza vaccine is safe and immunogenic in immunocompromised ferrets. Journal of Infectious Diseases 193(5): 677-684. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Abstract: Patients undergoing chemotherapy for cancer are highly susceptible to influenza virus infection. Prevention of influenza virus infection is complicated in the immunocompromised host because of suboptimal responses to the trivalent inactivated influenza vaccine (TIV). A new, live attenuated influenza vaccine (LAIV; FluMist) may offer a more effective alternative to TIV, but the safety of this LAIV in immunocompromised patients must first be established. In the present study, FluMist was administered to ferrets immunocompromised by treatment with dexamethasone and cytarabine. Ferrets exhibited no signs or symptoms attributable to FluMist, and nasal clearance of LAIV strains from immunocompromised ferrets was similar to that from control ferrets. Serum antibody responses against the vaccinating strains were analyzed as a measure of vaccine efficacy. Antibody titers to all 3 vaccine strains in immunocompromised ferrets were similar to those seen in mock-treated control ferrets, as assessed by microneutralization assay. These findings support the potential use of this vaccine in immunocompromised humans.
Descriptors: ferrets, blood antibodies, immunocompromised host, influenza A virus, influenza B virus, influenza vaccines, cytarabine, dexamethasone, immunosuppressive agents.

Lambkin, R., J.S. Oxford, S. Bossuyt, A. Mann, I.C. Metcalfe, C. Herzog, J.F. Viret, and R. Gluck (2004). Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine. Vaccine 22(31-32): 4390-4396. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: The proliferation of influenza viruses causes costly, recurrent, annual epidemics. Current vaccines, mainly administered parenterally, have been shown to be suboptimal in terms of efficacy, particularly where local IgA responses are concerned. Recent investigations of virosomes as delivery systems for viral HA and NA antigens have demonstrated an improved immune response. This paper investigates the efficacy of a novel virosome-based intranasal influenza vaccine by its ability to reduce disease symptoms and its effect on viral shedding in nasal secretions of immunised ferrets. The use of ferrets in the study of influenza vaccines is based on the good comparability between ferret and human response to the disease. Intranasal, as opposed to parenteral, administration of a trivalent virosome-based subunit vaccine adjuvanted with HLT provides an almost total prevention of virus shedding combined with a high level of immunological protection against homologous virus challenge. The ease of application of an intranasal vaccine may have positive repercussions in the adoption of influenza vaccinations, particularly in 'at-risk' groups.
Descriptors: ferrets, orthomyxoviridae infections, intranasal administration, influenza A virus, influenza B virus, influenza vaccines, orthomyxoviridae infections, virus shedding.

Langlois, I. (2005). Viral diseases of ferrets. Veterinary Clinics of North America. Exotic Animal Practice 8(1): 139-160. ISSN: 1094-9194.
NAL Call Number: SF997.5.E95 E97
Abstract: Distemper and rabies vaccination are highly recommended because of the almost invariable fatal outcome of these conditions. Vaccination should constitute an important part of a ferret's preventative medicine program. With the current and anticipated development and licensing of new vaccines, practitioners are invited to gain awareness of the latest vaccine information. Establishment of a practice vaccination protocol with regards to the site of administration of rabies and distemper vaccines is paramount to document any future abnormal tissue reactions. Influenza is the most common zoonotic disease that is seen in ferrets. Although it generally is benign in most ferrets, veterinarians must take this condition seriously. The characteristic continuous antigenic variation of this virus may lead to more virulent strains; the recent emergence of avian influenza virus outbreaks; and the increased susceptibility of elderly, young, and immunosuppressed individuals.
Descriptors: ferrets, viral diseases, distemper, rabies vaccination.

Ljungberg, K., C. Kolmskog, B. Wahren, G. van Amerongen, M. Baars, A. Osterhaus, A. Linde, and G. Rimmelzwaan (2002). DNA vaccination of ferrets with chimeric influenza A virus hemagglutinin (H3) genes. Vaccine 20(16): 2045-2052. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Recently a technology was established based on homologous recombination that allowed the rapid generation of chimeric HA genes of influenza viruses, containing the antigenic determinants obtained from various influenza virus A (H3N2) viruses. In the present report plasmids were generated using a H3 HA vector handle and the hypervariable regions of two genetically distinct influenza A H3N2 viruses, A/Stockholm/7/97 and A/Netherlands/18/94. In a ferret model it was shown that immunisation with plasmid DNA encoding chimeric HA indeed elicited antibody responses specific for the virus from which the hypervariable region with the antigenic determinants were obtained. After DNA-immunisation of the ferrets, protective immunity against infection with influenza virus A/Netherlands/18/94 was evaluated.
Descriptors: ferrets, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus, influenza vaccines, DNA vaccines, enzyme linked immunosorbent assay, lymphocyte activation, genetic recombination, T lymphocytes.

Maher, J.A. and J. DeStefano (2004). The ferret: An animal model to study influenza virus. Lab Animal 33(9): 50-53. ISSN: 0093-7355.
NAL Call Number: QL55.A1L33
Abstract: There has been much critical influenza research conducted in a little-known laboratory animal--the ferret. The authors review some of these findings, discuss the reasons the ferret often becomes a model for influenza infection, and compare the ferret with other animal models.
Descriptors: ferrets, animal models, orthomyxoviridae, influenza, literature review.

Maines, T.R., L.M. Chen, Y. Matsuoka, H. Chen, T. Rowe, J. Ortin, A. Falcon, T.H. Nguyen, l.Q. Mai, E.R. Sedyaningsih, S. Harun, T.M. Tumpey, R.O. Donis, N.J. Cox, K. Subbarao, and J.M. Katz (2006). Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proceedings of the National Academy of Sciences of the United States of America 103(32): 12121-12126. ISSN: 0027-8424.
Abstract: Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait.
Descriptors: ferrets virology, influenza A virus, H5N1, metabolism, human transmission, human virology, reassortant viruses, metabolism, disease models, virus replication.

Mann, A., A.C. Marriott, S. Balasingam, R. Lambkin, J.S. Oxford, and N.J. Dimmock (2006). Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection. Vaccine 24(20): 4290-4296. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Defective interfering (DI) virus RNAs result from major deletions in full-length viral RNAs that occur spontaneously during de novo RNA synthesis. These RNAs are packaged into virions that are by definition non-infectious, and are delivered to cells normally targeted by the virion. DI RNAs can only replicate with the aid of a coinfecting infectious helper virus, but the small size of DI RNA allows more copies of it to be made than of its full-length counterpart, so the cell produces defective virions in place of infectious progeny. In line with this scenario, the expected lethal disease in an influenza A virus-mouse model is made subclinical by administration of DI virus, but animals develop solid immunity to the infecting virus. Hence DI virus has been called an 'interfering vaccine'. Because interfering vaccine acts intracellularly and at a molecular level, it should be effective against all influenza A viruses regardless of subtype. Here we have used the ferret, widely acknowledged as the best model for human influenza. We show that an interfering vaccine with defective RNAs from an H3N8 virus almost completely abolished clinical disease caused by A/Sydney/5/97 (H3N2), with abrogation of fever and significant reductions in clinical signs of illness. Animals recovered fully and were solidly immune to reinfection, in line with the view that treatment converts the otherwise virulent disease into a subclinical and immunizing infection.
Descriptors: influenza vaccines, administration, dosage, influenza virus A immunology, ferrets, mice, orthomyxoviridae infections, immunology.

Martina, B.E.E., B.L. Haagmans, and T. Kuiken (2003). SARS virus infection of cats and ferrets. Nature 425(6961): 915. ISSN: 0028-0836.
Abstract: The susceptibility of the domestic cat (Felis domesticus) and the ferret (Mustela furo) to severe acute respiratory syndrome (SARS) was investigated. Cats and ferrets inoculated with SARS coronavirus were susceptible to infection and efficiently transmitted the virus to previously uninfected animals that were housed with them. These species might, therefore, be useful as animal models to evaluate antiviral drugs or vaccine candidates against SARS. The ease with which the 2 distantly related carnivores can be infected suggests that the reservoir for SARS may involve a range of species.
Descriptors: ferrets, cats, SARS, virus infection, acute respiratory syndrome, transmission, reservoir.

Martinez, J., A.J. Ramis, M. Reinacher, and D. Perpinan (2006). Detection of feline infectious peritonitis virus-like antigen in ferrets. Veterinary Record 158(15): 523. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: ferrets, antigens, detection, coronavirus, feline infectious peritonitis diagnosis, epidemiology, virology.

Mishin, V.P., M.S. Nedyalkova, F.G. Hayden, and L.V. Gubareva (2005). Protection afforded by intranasal immunization with the neuraminidase-lacking mutant of influenza A virus in a ferret model. Vaccine 23(22): 2922-2927. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Protective efficacy of the intranasal immunization with the neuraminidase (NA)-deficient mutant of the influenza A virus was investigated in ferrets. Despite the highly attenuated replication in vivo, the mutant completely protected the animals against the wild type virus challenge. When challenge was done with antigenic drift variants, significant reductions in the viral titers, inflammatory cell counts, and protein concentrations were observed in the nasal washes of the immunized animals. The genetically engineered NA-deficient mutant also protected animals against the challenge and induced humoral immune response against the foreign protein that replaced the NA. We conclude that the NA as antigen is dispensable in the live attenuated influenza virus vaccine and that the NA-lacking mutant can be used as a virus vector.
Descriptors: ferrets, influenza A virus, vaccine administration, neuraminidase genetics, orthomyxoviridae infections, intranasal administration, virus enzymology, genetics, animal models.

Miwa, Y., S. Matsunaga, M. Ando, H. Nakayama, K. Uetsuka, H. Nakamura, and H. Ogawa (2005). Spontaneous Aleutian disease in a ferret infected with the ferret-derived Aleutian-disease virus strain. Journal of the Japan Veterinary Medical Association 58(7): 484-487. ISSN: 0446-6454.
Descriptors: ferret, Aleutian disease, spontaneous, clinical aspects.
Language of Text: Japanese; Summary in English.

Moore, G.E., N.W. Glickman, M.P. Ward, K.S. Engler, H.B. Lewis, and L.T. Glickman (2005). Incidence of and risk factors for adverse events associated with distemper and rabies vaccine administration in ferrets. Journal of the American Veterinary Medical Association 226(6): 909-912. ISSN: 0003-1488.
NAL Call Number: 41.8 Am3
Abstract: OBJECTIVE: To determine incidence of and risk factors for adverse events associated with distemper and rabies vaccine administration in ferrets. DESIGN: Retrospective cohort study. ANIMALS: 3,587 ferrets that received a rabies or distemper vaccine between January 1, 2002, and December 31, 2003. PROCEDURES: Electronic medical records were searched for possible vaccine-associated adverse events. Adverse events were classified by attending veterinarians as nonspecific vaccine reactions, allergic reactions, or anaphylaxis. Patient information that was collected included age, weight, sex, cumulative number of distemper and rabies vaccinations received, clinical signs, and treatment. The association between potential risk factors and occurrence of an adverse event was estimated with logistic regression. RESULTS: 30 adverse events were recorded. The adverse event incidence rates for administration of rabies vaccine alone, distemper vaccine alone, and rabies and distemper vaccines together were 0.51%, 1.00%, and 0.85%, respectively. These rates were not significantly different. All adverse events occurred immediately following vaccine administration and most commonly consisted of vomiting and diarrhea (52%) or vomiting alone (31%). Age, sex, and body weight were not significantly associated with occurrence of adverse events, but adverse event incidence rate increased as the cumulative number of distemper or rabies vaccinations received increased. In multivariate logistic regression analysis, only the cumulative number of distemper vaccinations received was significantly associated with the occurrence of an adverse event. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in ferrets, the risk of vaccine-associated adverse events was primarily associated with an increase in the number of distemper vaccinations.
Descriptors: diarrhea, ferrets, rabies vaccines, adverse effects of viral vaccines, distemper virus, canine immunology, logistic models, rabies virus, vomiting.

Peltola, V.T., K.L. Boyd, J.L. McAuley, J.E. Rehg, and J.A. McCullers (2006). Bacterial sinusitis and otitis media following influenza virus infection in ferrets. Infection and Immunity 74(5): 2562-2567. ISSN: 1098-5522.
NAL Call Number: QR1.I57
Abstract: Streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and pneumonia. Many of these infections result from antecedent influenza virus infections. In this study we sought to determine whether the frequency and character of secondary pneumococcal infections differed depending on the strain of influenza virus that preceded bacterial challenge. In young ferrets infected with influenza virus and then challenged with pneumococcus, influenza viruses of any subtype increased bacterial colonization of the nasopharynx. Nine out of 10 ferrets infected with H3N2 subtype influenza A viruses developed either sinusitis or otitis media, while only 1 out of 11 ferrets infected with either an H1N1 influenza A virus or an influenza B virus did so. These data may partially explain why bacterial complication rates are higher during seasons when H3N2 viruses predominate. This animal model will be useful for further study of the mechanisms that underlie viral-bacterial synergism.
Descriptors: ferrets, bacterial infection, virus infection, sinusitis, pneumonia, viral-bacterial synergism.

Pennick, K.E., M.A. Stevenson, K.S. Latimer, B.W. Ritchie, and C.R. Gregory (2005). Persistent viral shedding during asymptomatic Aleutian mink disease parvoviral infection in a ferret. Journal of Veterinary Diagnostic Investigation 17(6): 594-597. ISSN: 1040-6387.
NAL Call Number: SF774.J68
Abstract: A 2-year-old domestic ferret that appeared clinically healthy was repeatedly seropositive for Aleutian mink disease parvovirus (ADV) over a 2-year observation period. Antibody titers, determined by counter-immunoelectrophoresis, ranged from 1024 to 4096. Viral DNA also was identified in serum, urine, feces, and blood cell fractions by polymerase chain reaction analysis. Ultimately, DNA in situ hybridization revealed ADV DNA in histologic sections of various tissues and organs. These data indicate that this asymptomatic ferret was persistently infected with ADV.
Descriptors: ferrets, Aleutian mink disease, virology, carrier state, virus shedding, antibodies, blood, physiopathology, DNA, physiology, kidney, liver, lung, spleen, urine.

Stanton, J., L. Givens, J. Evermann, and C. Brown (2003). Immunohistochemical analysis of two strains of lion (Panthera leo)-adapted canine distemper virus in ferrets (Mustela putorius furo). Veterinary Pathology 40(4): 464-467. ISSN: 0300-9858.
NAL Call Number: 41.8 P27
Descriptors: Panthera leo, canine distemper virus, cross species infection, immunohistochemical analysis, ferrets, lions.

Suguitan, A. L, J. McAuliffe, K. Mills L, H. Jin, G. Duke, B. Lu, C. Luke J, B. Murphy, D. Swayne E, G. Kemble, and K. Subbarao (2006). Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets. PLoS Medicine 3(9): E360. ISSN: 1549-1676.
Abstract: BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.
Descriptors: ferrets, mice, live attenuated influenza virus, H5N1, vaccine, cross protection.

Sweet, C., K.J. Jakeman, K. Bush, P.C. Wagaman, L.A. McKown, A.J. Streeter, D. Desai Krieger, P. Chand, and Y.S. Babu (2002). Oral administration of cyclopentane neuraminidase inhibitors protects ferrets against influenza virus infection. Antimicrobial Agents and Chemotherapy 46(4): 996-1004. ISSN: 0066-4804.
Abstract: Several cyclopentane inhibitors of influenza virus neuraminidase that have inhibitory activities in tissue culture similar to those of zanamivir and oseltamivir have recently been described. These new inhibitors have been examined for efficacy against a virulent H3N2 influenza virus when administered orally to infected ferrets. Preliminary studies indicated that oral administration of BCX-1923, BCX-1827, or BCX-1812 (RWJ-270201) at a dose of 5 or 25 mg/kg of body weight was active in ferrets in reducing respiratory and constitutional signs and symptoms, but these antivirals affected virus titers in the upper and lower respiratory tracts only marginally. Of the three compounds, BCX-1812 seemed to be the most efficacious and was examined further at higher doses of 30 and 100 mg/kg. These doses significantly reduced peak virus titers in nasal washes and total virus shedding as measured by areas under the curve. Virus titers in lung homogenates were also reduced compared to those in controls, but the difference was not statistically significant. As was observed with BCX-1812 at lower doses, the nasal inflammatory cellular response, fever, and nasal signs were reduced while ferret activity was not, with activity remaining similar to uninfected animals.
Descriptors: ferrets, antiviral agents, cyclopentanes, enzyme inhibitors, influenza A virus, neuraminidase antagonists and inhibitors, orthomyxoviridae infections, acetamides, body temperature, cell count, cyclopentanes, hemagglutination inhibition tests, lung microbiology, nasal cavity cytology.

Ter Meulen, J., A.B.H. Bakker, E.N. Van Den Brink, G.J. Weverling, B.E.E. Martina, B.L. Haagmans, T. Kuiken, J. De Kruif, W. Preiser, W. Spaan, H.R. Gelderblom, J. Goudsmit, and A.D.M.E. Osterhaus (2004). Human monoclonal antibody as prophylaxis for sars coronavirus infection in ferrets. Lancet 363(9427): 2139-2141. ISSN: 0099-5355.
Descriptors: ferrets, SARS infection, coronavirus infection, human monoclonal antibody, prophylaxis, severe acute reapiratory syndrome, animal model.

von Messling, V., C. Springfeld, P. Devaux, and R. Cattaneo (2003). A ferret model of canine distemper virus virulence and immunosuppression. Journal of Virology 77(23): 12579-12591. ISSN: 0022-538X.
NAL Call Number: QR360.J6
Abstract: Canine distemper virus (CDV) infects many carnivores, including ferrets and dogs, and is the member of the Morbillivirus genus most easily amenable to experimentation in a homologous small-animal system. To gain insights into the determinants of CDV pathogenesis, we isolated a strain highly virulent for ferrets by repeated passaging in these animals. Sequence comparison of the genome of this strain with that of its highly attenuated precursor revealed 19 mutations distributed almost evenly in the six genes. We then recovered a virus from a cDNA copy of the virulent CDV strain's consensus sequence by using a modified reverse genetics system based on B cells. We infected ferrets with this virus and showed that it fully retained virulence as measured by the timing of rash appearance, disease onset, and death. Body temperature, leukocyte number, lymphocyte proliferation activity, and cell-associated viremia also had similar kinetics. We then addressed the question of the relative importance of the envelope and other viral constituents for virulence. Viruses in which the envelope genes (matrix, fusion, and hemagglutinin) of the virulent strain were combined with the other genes of the attenuated strain caused severe rash and fever even if the disease onset was delayed. Viruses in which the nucleocapsid, polymerase, and phosphoprotein genes (coding also for the V and C proteins) of the virulent strain were combined with the envelope genes of the attenuated strain caused milder signs of disease. Thus, virulence-inducing mutations have accumulated throughout the genome.
Descriptors: ferrets, animal disease models, distemper virus, canine pathogenicity, immunosuppression, b lymphocytes immunology, DNA, canine genetics, vero cells, virulence genetics.

von Messling, V., C. Springfeld, P. Devaux, and R. Cattaneo (2003). A ferret model of canine distemper virus virulence and immunosuppression. Journal of Virology 77(23): 12579-12591. ISSN: 0022-538X.
NAL Call Number: QR360.J6
Descriptors: ferret, animal model, canine distemper, virulence, immunosuppression, Morbillivirus.

Vos, A., T. Muller, J. Cox, L. Neubert, and A.R. Fooks (2004). Susceptibility of ferrets (Mustela putorius furo) to experimentally induced rabies with European Bat Lyssaviruses (EBLV). Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health 51(2): 55-60. ISSN: 0931-1793.
Abstract: Twenty ferrets (Mustela putorius furo) were inoculated by intramuscular (i.m.) injection with European Bat Lyssaviruses (EBLV) type-1 and 2 using 10(4.0) foci-forming units (FFU) EBLV-2 (n = 6), 10(4.0) FFU EBLV-1 (n = 7) and 10(6.0) FFU EBLV-1 (n = 7). Furthermore, 15 mice received 10(2.5) FFU EBLV-2 (n = 5), 10(2.5) FFU EBLV-1 (n = 5) and 10(4.5) FFU EBLV-1 (n = 5) by i.m. inoculation. All ferrets and mice receiving the higher dose of EBLV-1 succumbed to infection. In contrast, only three of seven ferrets and two of five mice inoculated experimentally with the lower EBLV-1 dose died. By comparison, all of the EBLV-2 infected ferrets and four of five mice survived infection. All 20 infected ferrets seroconverted. Using sensitive molecular tools, the virus was detected in different tissues, but it could not be found in any saliva samples taken during the 84-day observation period.
Descriptors: ferrets, lyssavirus, rhabdoviridae infections, DNA, viral analysis, disease susceptibility.

Wise, A.G., M. Kiupel, and R.K. Maes (2006). Molecular characterization of a novel coronavirus associated with epizootic catarrhal enteritis (ECE) in ferrets. Virology 349(1): 164-174. ISSN: 0042-6822.
Abstract: A novel coronavirus, designated as ferret enteric coronavirus (FECV), was identified in feces of domestic ferrets clinically diagnosed with epizootic catarrhal enteritis (ECE). Initially, partial sequences of the polymerase, spike, membrane protein, and nucleocapsid genes were generated using coronavirus consensus PCR assays. Subsequently, the complete sequences of the nucleocapsid gene and the last two open reading frames at the 3' terminus of the FECV genome were obtained. Phylogenetic analyses based on predicted partial amino acid sequences of the polymerase, spike, and membrane proteins, and full sequence of the nucleocapsid protein showed that FECV is genetically most closely related to group 1 coronaviruses. FECV is more similar to feline coronavirus, porcine transmissible gastroenteritis virus, and canine coronavirus than to porcine epidemic diarrhea virus and human coronavirus 229E. Molecular data presented in this study provide the first genetic evidence for a new coronavirus associated with clinical cases of ECE.
Descriptors: ferrets, coronavirus, enteritis, amino acid sequence, infections epidemiology, canine genetics, feline genetics, epizootic catarrhal enteritis (ECE).

Zitzow, L.A., T. Rowe, T. Morken, W.J. Shieh, S. Zaki, and J.M. Katz (2002). Pathogenesis of avian influenza A (H5N1) viruses in ferrets. Journal of Virology 76(9): 4420-4429. ISSN: 0022-538X.
NAL Call Number: QR360.J6
Abstract: Highly pathogenic avian influenza A H5N1 viruses caused outbreaks of disease in domestic poultry and humans in Hong Kong in 1997. Direct transmission of the H5N1 viruses from birds to humans resulted in 18 documented cases of respiratory illness, including six deaths. Here we evaluated two of the avian H5N1 viruses isolated from humans for their ability to replicate and cause disease in outbred ferrets. A/Hong Kong/483/97 virus was isolated from a fatal case and was highly pathogenic in the BALB/c mouse model, whereas A/Hong Kong/486/97 virus was isolated from a case with mild illness and exhibited a low-pathogenicity phenotype in mice. Ferrets infected intranasally with 10(7) 50% egg infectious doses (EID(50)) of either H5N1 virus exhibited severe lethargy, fever, weight loss, transient lymphopenia, and replication in the upper and lower respiratory tract, as well as multiple systemic organs, including the brain. Gastrointestinal symptoms were seen in some animals. In contrast, weight loss and severe lethargy were not noted in ferrets infected with 10(7) EID(50) of two recent human H3N2 viruses, although these viruses were also isolated from the brains, but not other extrapulmonary organs, of infected animals. The results demonstrate that both H5N1 viruses were highly virulent in the outbred ferret model, unlike the differential pathogenicity documented in inbred BALB/c mice. We propose the ferret as an alternative model system for the study of these highly pathogenic avian viruses.
Descriptors: disease models, ferrets, influenza physiopathology, influenza A virus, avian pathogenicity, adolescent, child, influenza pathology and virology, lung pathology and virology, virulence, virus replication.

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