Previous Article | Next Article 
Journal of Virology, April 1999, p. 3184-3189, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Biological Heterogeneity, Including Systemic
Replication in Mice, of H5N1 Influenza A Virus Isolates from Humans
in Hong Kong
Peng
Gao,1
Shinji
Watanabe,1,2
Toshihiro
Ito,3
Hideo
Goto,1
Krisna
Wells,1
Martha
McGregor,1
A. James
Cooley,1 and
Yoshihiro
Kawaoka1,*
Department of Pathobiological Sciences,
School of Veterinary Medicine, University of Wisconsin
Madison,
Madison, Wisconsin 53706,1 and
Laboratory of Microbiology, Department of Disease Control,
Graduate School of Veterinary Medicine, Hokkaido University, Sapporo
060-0818,2 and Department of Veterinary
Public Health, Faculty of Agriculture, Tottori University, Tottori
680-0945,3 Japan
Received 25 September 1998/Accepted 23 December 1998
An H5N1 avian influenza A virus was transmitted to humans in Hong
Kong in 1997. Although the virus causes systemic infection and is
highly lethal in chickens because of the susceptibility of the
hemagglutinin to furin and PC6 proteases, it is not known whether it
also causes systemic infection in humans. The clinical outcomes of
infection in Hong Kong residents ranged widely, from mild respiratory
disease to multiple organ failure leading to death. Therefore, to
understand the pathogenesis of influenza due to these H5N1 isolates, we
investigated their virulence in mice. The results identified two
distinct groups of viruses: group 1, for which the dose lethal for 50%
of mice (MLD50) was between 0.3 and 11 PFU, and group 2, for which the MLD50 was more than 103 PFU. One
day after intranasal inoculation of mice with 100 PFU of group 1 viruses, the virus titer in lungs was 107 PFU/g or 3 log
units higher than that for group 2 viruses. Both types of viruses had
replicated to high titers (>106 PFU/g) in the lungs by day
3 and maintained these titers through day 6. More importantly, only the
group 1 viruses caused systemic infection, replicating in
nonrespiratory organs, including the brain. Immunohistochemical
analysis demonstrated the replication of a group 1 virus in brain
neurons and glial cells and in cardiac myofibers. Phylogenetic analysis
of all viral genes showed that both groups of Hong Kong H5N1 viruses
had formed a lineage distinct from those of other viruses and that
genetic reassortment between H5N1 and H1 or H3 human viruses had not
occurred. Since mice and humans harbor both the furin and the PC6
proteases, we suggest that the virulence mechanism responsible for the
lethality of influenza viruses in birds also operates in mammalian
hosts. The failure of some H5N1 viruses to produce systemic infection
in our model indicates that multiple, still-to-be-identified, factors contribute to the severity of H5N1 infection in mammals. In addition, the ability of these viruses to produce systemic infection in mice and
the clear differences in pathogenicity among the isolates studied here
indicate that this system provides a useful model for studying the
pathogenesis of avian influenza virus infection in mammals.
*
Corresponding author. Mailing address: Department of
Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin
Madison, 2015 Linden Dr. West, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail:
kawaokay{at}svm.vetmed.wisc.edu.
Journal of Virology, April 1999, p. 3184-3189, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Tate, M. D., Deng, Y.-M., Jones, J. E., Anderson, G. P., Brooks, A. G., Reading, P. C.
(2009). Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection. J. Immunol.
183: 7441-7450
[Abstract]
[Full Text]
-
Fornek, J. L., Gillim-Ross, L., Santos, C., Carter, V., Ward, J. M., Cheng, L. I., Proll, S., Katze, M. G., Subbarao, K.
(2009). A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice. J. Virol.
83: 11102-11115
[Abstract]
[Full Text]
-
Belser, J. A., Wadford, D. A., Xu, J., Katz, J. M., Tumpey, T. M.
(2009). Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract. J. Virol.
83: 7075-7084
[Abstract]
[Full Text]
-
Szretter, K. J., Gangappa, S., Belser, J. A., Zeng, H., Chen, H., Matsuoka, Y., Sambhara, S., Swayne, D. E., Tumpey, T. M., Katz, J. M.
(2009). Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J. Virol.
83: 5825-5834
[Abstract]
[Full Text]
-
Van Hoeven, N., Belser, J. A., Szretter, K. J., Zeng, H., Staeheli, P., Swayne, D. E., Katz, J. M., Tumpey, T. M.
(2009). Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding. J. Virol.
83: 2851-2861
[Abstract]
[Full Text]
-
Yen, H.-L., Aldridge, J. R., Boon, A. C. M., Ilyushina, N. A., Salomon, R., Hulse-Post, D. J., Marjuki, H., Franks, J., Boltz, D. A., Bush, D., Lipatov, A. S., Webby, R. J., Rehg, J. E., Webster, R. G.
(2009). Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread. Proc. Natl. Acad. Sci. USA
106: 286-291
[Abstract]
[Full Text]
-
Gillim-Ross, L., Santos, C., Chen, Z., Aspelund, A., Yang, C.-F., Ye, D., Jin, H., Kemble, G., Subbarao, K.
(2008). Avian Influenza H6 Viruses Productively Infect and Cause Illness in Mice and Ferrets. J. Virol.
82: 10854-10863
[Abstract]
[Full Text]
-
Korteweg, C., Gu, J.
(2008). Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans. Am. J. Pathol.
172: 1155-1170
[Abstract]
[Full Text]
-
Zeng, H., Goldsmith, C., Thawatsupha, P., Chittaganpitch, M., Waicharoen, S., Zaki, S., Tumpey, T. M., Katz, J. M.
(2007). Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells. J. Virol.
81: 12439-12449
[Abstract]
[Full Text]
-
Mukhtar, M. M., Rasool, S. T., Song, D., Zhu, C., Hao, Q., Zhu, Y., Wu, J.
(2007). Origin of highly pathogenic H5N1 avian influenza virus in China and genetic characterization of donor and recipient viruses. J. Gen. Virol.
88: 3094-3099
[Abstract]
[Full Text]
-
Belser, J. A., Lu, X., Maines, T. R., Smith, C., Li, Y., Donis, R. O., Katz, J. M., Tumpey, T. M.
(2007). Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans. J. Virol.
81: 11139-11147
[Abstract]
[Full Text]
-
Peiris, J. S. M., de Jong, M. D., Guan, Y.
(2007). Avian Influenza Virus (H5N1): a Threat to Human Health. Clin. Microbiol. Rev.
20: 243-267
[Abstract]
[Full Text]
-
Szretter, K. J., Gangappa, S., Lu, X., Smith, C., Shieh, W.-J., Zaki, S. R., Sambhara, S., Tumpey, T. M., Katz, J. M.
(2007). Role of Host Cytokine Responses in the Pathogenesis of Avian H5N1 Influenza Viruses in Mice. J. Virol.
81: 2736-2744
[Abstract]
[Full Text]
-
Shinya, K., Watanabe, S., Ito, T., Kasai, N., Kawaoka, Y.
(2007). Adaptation of an H7N7 equine influenza A virus in mice. J. Gen. Virol.
88: 547-553
[Abstract]
[Full Text]
-
Mase, M., Tanimura, N., Imada, T., Okamatsu, M., Tsukamoto, K., Yamaguchi, S.
(2006). Recent H5N1 avian Influenza A virus increases rapidly in virulence to mice after a single passage in mice. J. Gen. Virol.
87: 3655-3659
[Abstract]
[Full Text]
-
Li, Z., Jiang, Y., Jiao, P., Wang, A., Zhao, F., Tian, G., Wang, X., Yu, K., Bu, Z., Chen, H.
(2006). The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. J. Virol.
80: 11115-11123
[Abstract]
[Full Text]
-
Gillim-Ross, L., Subbarao, K.
(2006). Emerging Respiratory Viruses: Challenges and Vaccine Strategies. Clin. Microbiol. Rev.
19: 614-636
[Abstract]
[Full Text]
-
Chen, H., Li, Y., Li, Z., Shi, J., Shinya, K., Deng, G., Qi, Q., Tian, G., Fan, S., Zhao, H., Sun, Y., Kawaoka, Y.
(2006). Properties and Dissemination of H5N1 Viruses Isolated during an Influenza Outbreak in Migratory Waterfowl in Western China.. J. Virol.
80: 5976-5983
[Abstract]
[Full Text]
-
Gabriel, G., Dauber, B., Wolff, T., Planz, O., Klenk, H.-D., Stech, J.
(2005). The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc. Natl. Acad. Sci. USA
102: 18590-18595
[Abstract]
[Full Text]
-
Maines, T. R., Lu, X. H., Erb, S. M., Edwards, L., Guarner, J., Greer, P. W., Nguyen, D. C., Szretter, K. J., Chen, L.-M., Thawatsupha, P., Chittaganpitch, M., Waicharoen, S., Nguyen, D. T., Nguyen, T., Nguyen, H. H. T., Kim, J.-H., Hoang, L. T., Kang, C., Phuong, L. S., Lim, W., Zaki, S., Donis, R. O., Cox, N. J., Katz, J. M., Tumpey, T. M.
(2005). Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals. J. Virol.
79: 11788-11800
[Abstract]
[Full Text]
-
Li, Z., Chen, H., Jiao, P., Deng, G., Tian, G., Li, Y., Hoffmann, E., Webster, R. G., Matsuoka, Y., Yu, K.
(2005). Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model. J. Virol.
79: 12058-12064
[Abstract]
[Full Text]
-
Shinya, K., Hatta, M., Yamada, S., Takada, A., Watanabe, S., Halfmann, P., Horimoto, T., Neumann, G., Kim, J. H., Lim, W., Guan, Y., Peiris, M., Kiso, M., Suzuki, T., Suzuki, Y., Kawaoka, Y.
(2005). Characterization of a Human H5N1 Influenza A Virus Isolated in 2003. J. Virol.
79: 9926-9932
[Abstract]
[Full Text]
-
Nguyen, D. C., Uyeki, T. M., Jadhao, S., Maines, T., Shaw, M., Matsuoka, Y., Smith, C., Rowe, T., Lu, X., Hall, H., Xu, X., Balish, A., Klimov, A., Tumpey, T. M., Swayne, D. E., Huynh, L. P. T., Nghiem, H. K., Nguyen, H. H. T., Hoang, L. T., Cox, N. J., Katz, J. M.
(2005). Isolation and Characterization of Avian Influenza Viruses, Including Highly Pathogenic H5N1, from Poultry in Live Bird Markets in Hanoi, Vietnam, in 2001. J. Virol.
79: 4201-4212
[Abstract]
[Full Text]
-
Lee, C.-W., Suarez, D. L., Tumpey, T. M., Sung, H.-W., Kwon, Y.-K., Lee, Y.-J., Choi, J.-G., Joh, S.-J., Kim, M.-C., Lee, E.-K., Park, J.-M., Lu, X., Katz, J. M., Spackman, E., Swayne, D. E., Kim, J.-H.
(2005). Characterization of Highly Pathogenic H5N1 Avian Influenza A Viruses Isolated from South Korea. J. Virol.
79: 3692-3702
[Abstract]
[Full Text]
-
de Jong, M. D., Cam, B. V., Qui, P. T., Hien, V. M., Thanh, T. T., Hue, N. B., Beld, M., Phuong, L. T., Khanh, T. H., Chau, N. V. V., Hien, T. T., Ha, D. Q., Farrar, J.
(2005). Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma. NEJM
352: 686-691
[Abstract]
[Full Text]
-
Govorkova, E. A., Rehg, J. E., Krauss, S., Yen, H.-L., Guan, Y., Peiris, M., Nguyen, T. D., Hanh, T. H., Puthavathana, P., Long, H. T., Buranathai, C., Lim, W., Webster, R. G., Hoffmann, E.
(2005). Lethality to Ferrets of H5N1 Influenza Viruses Isolated from Humans and Poultry in 2004. J. Virol.
79: 2191-2198
[Abstract]
[Full Text]
-
Puthavathana, P., Auewarakul, P., Charoenying, P. C., Sangsiriwut, K., Pooruk, P., Boonnak, K., Khanyok, R., Thawachsupa, P., Kijphati, R., Sawanpanyalert, P.
(2005). Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand. J. Gen. Virol.
86: 423-433
[Abstract]
[Full Text]
-
Karasin, A. I., West, K., Carman, S., Olsen, C. W.
(2004). Characterization of Avian H3N3 and H1N1 Influenza A Viruses Isolated from Pigs in Canada. J. Clin. Microbiol.
42: 4349-4354
[Abstract]
[Full Text]
-
Lipatov, A. S., Govorkova, E. A., Webby, R. J., Ozaki, H., Peiris, M., Guan, Y., Poon, L., Webster, R. G.
(2004). Influenza: Emergence and Control. J. Virol.
78: 8951-8959
[Full Text]
-
Chen, H., Deng, G., Li, Z., Tian, G., Li, Y., Jiao, P., Zhang, L., Liu, Z., Webster, R. G., Yu, K.
(2004). The evolution of H5N1 influenza viruses in ducks in southern China. Proc. Natl. Acad. Sci. USA
101: 10452-10457
[Abstract]
[Full Text]
-
Shinya, K., Fujii, Y., Ito, H., Ito, T., Kawaoka, Y.
(2004). Characterization of a Neuraminidase-Deficient Influenza A Virus as a Potential Gene Delivery Vector and a Live Vaccine. J. Virol.
78: 3083-3088
[Abstract]
[Full Text]
-
Tumpey, T. M., Garcia-Sastre, A., Taubenberger, J. K., Palese, P., Swayne, D. E., Basler, C. F.
(2004). Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Proc. Natl. Acad. Sci. USA
101: 3166-3171
[Abstract]
[Full Text]
-
Matsuda, K., Park, C. H., Sunden, Y., Kimura, T., Ochiai, K., Kida, H., Umemura, T.
(2004). The Vagus Nerve is One Route of Transneural Invasion for Intranasally Inoculated Influenza A Virus in Mice. Vet Pathol
41: 101-107
[Abstract]
[Full Text]
-
Hatta, M., Kawaoka, Y.
(2003). The NB Protein of Influenza B Virus Is Not Necessary for Virus Replication In Vitro. J. Virol.
77: 6050-6054
[Abstract]
[Full Text]
-
Kuiken, T., Rimmelzwaan, G. F., Van Amerongen, G., Osterhaus, A. D. M. E.
(2003). Pathology of Human Influenza A (H5N1) Virus Infection in Cynomolgus Macaques (Macaca fascicularis). Vet Pathol
40: 304-310
[Abstract]
[Full Text]
-
Lipatov, A. S., Krauss, S., Guan, Y., Peiris, M., Rehg, J. E., Perez, D. R., Webster, R. G.
(2003). Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001. J. Virol.
77: 3816-3823
[Abstract]
[Full Text]
-
Tumpey, T. M., Garcia-Sastre, A., Mikulasova, A., Taubenberger, J. K., Swayne, D. E., Palese, P., Basler, C. F.
(2002). Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proc. Natl. Acad. Sci. USA
99: 13849-13854
[Abstract]
[Full Text]
-
Tumpey, T. M., Suarez, D. L., Perkins, L. E. L., Senne, D. A., Lee, J.-g., Lee, Y.-J., Mo, I.-P., Sung, H.-W., Swayne, D. E.
(2002). Characterization of a Highly Pathogenic H5N1 Avian Influenza A Virus Isolated from Duck Meat. J. Virol.
76: 6344-6355
[Abstract]
[Full Text]
-
Zitzow, L. A., Rowe, T., Morken, T., Shieh, W.-J., Zaki, S., Katz, J. M.
(2002). Pathogenesis of Avian Influenza A (H5N1) Viruses in Ferrets. J. Virol.
76: 4420-4429
[Abstract]
[Full Text]
-
Govorkova, E. A., Leneva, I. A., Goloubeva, O. G., Bush, K., Webster, R. G.
(2001). Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses. Antimicrob. Agents Chemother.
45: 2723-2732
[Abstract]
[Full Text]
-
Hatta, M., Gao, P., Halfmann, P., Kawaoka, Y.
(2001). Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses. Science
293: 1840-1842
[Abstract]
[Full Text]
-
Rimmelzwaan, G. F., Kuiken, T., van Amerongen, G., Bestebroer, T. M., Fouchier, R. A. M., Osterhaus, A. D. M. E.
(2001). Pathogenesis of Influenza A (H5N1) Virus Infection in a Primate Model. J. Virol.
75: 6687-6691
[Abstract]
[Full Text]
-
Tumpey, T. M., Renshaw, M., Clements, J. D., Katz, J. M.
(2001). Mucosal Delivery of Inactivated Influenza Vaccine Induces B-Cell-Dependent Heterosubtypic Cross-Protection against Lethal Influenza A H5N1 Virus Infection. J. Virol.
75: 5141-5150
[Abstract]
[Full Text]
-
Massin, P., van der Werf, S., Naffakh, N.
(2001). Residue 627 of PB2 Is a Determinant of Cold Sensitivity in RNA Replication of Avian Influenza Viruses. J. Virol.
75: 5398-5404
[Abstract]
[Full Text]
-
Yao, Y., Mingay, L. J., McCauley, J. W., Barclay, W. S.
(2001). Sequences in Influenza A Virus PB2 Protein That Determine Productive Infection for an Avian Influenza Virus in Mouse and Human Cell Lines. J. Virol.
75: 5410-5415
[Abstract]
[Full Text]
-
Brown, E. G., Liu, H., Kit, L. C., Baird, S., Nesrallah, M.
(2001). Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes. Proc. Natl. Acad. Sci. USA
10.1073/pnas.111165798v1
[Abstract]
[Full Text]
-
Leneva, I. A., Goloubeva, O., Fenton, R. J., Tisdale, M., Webster, R. G.
(2001). Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals. Antimicrob. Agents Chemother.
45: 1216-1224
[Abstract]
[Full Text]
-
Perkins, L. E. L., Swayne, D. E.
(2001). Pathobiology of A/Chicken/Hong Kong/220/97 (H5N1) Avian Influenza Virus in Seven Gallinaceous Species. Vet Pathol
38: 149-164
[Abstract]
[Full Text]
-
Horimoto, T., Kawaoka, Y.
(2001). Pandemic Threat Posed by Avian Influenza A Viruses. Clin. Microbiol. Rev.
14: 129-149
[Abstract]
[Full Text]
-
Katz, J. M., Lu, X., Tumpey, T. M., Smith, C. B., Shaw, M. W., Subbarao, K.
(2000). Molecular Correlates of Influenza A H5N1 Virus Pathogenesis in Mice. J. Virol.
74: 10807-10810
[Abstract]
[Full Text]
-
ONeill, E., Krauss, S. L., Riberdy, J. M., Webster, R. G., Woodland, D. L.
(2000). Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J. Gen. Virol.
81: 2689-2696
[Abstract]
[Full Text]
-
Karasin, A. I., Brown, I. H., Carman, S., Olsen, C. W.
(2000). Isolation and Characterization of H4N6 Avian Influenza Viruses from Pigs with Pneumonia in Canada. J. Virol.
74: 9322-9327
[Abstract]
[Full Text]
-
Nishimura, H., Itamura, S., Iwasaki, T., Kurata, T., Tashiro, M.
(2000). Characterization of human influenza A (H5N1) virus infection in mice: neuro-, pneumo- and adipotropic infection. J. Gen. Virol.
81: 2503-2510
[Abstract]
[Full Text]
-
Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. A., Cook, D. I.
(2000). Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia. Proc. Natl. Acad. Sci. USA
10.1073/pnas.160041997v1
[Abstract]
[Full Text]
-
Hoffmann, E., Stech, J., Leneva, I., Krauss, S., Scholtissek, C., Chin, P. S., Peiris, M., Shortridge, K. F., Webster, R. G.
(2000). Characterization of the Influenza A Virus Gene Pool in Avian Species in Southern China: Was H6N1 a Derivative or a Precursor of H5N1?. J. Virol.
74: 6309-6315
[Abstract]
[Full Text]
-
Cauthen, A. N., Swayne, D. E., Schultz-Cherry, S., Perdue, M. L., Suarez, D. L.
(2000). Continued Circulation in China of Highly Pathogenic Avian Influenza Viruses Encoding the Hemagglutinin Gene Associated with the 1997 H5N1 Outbreak in Poultry and Humans. J. Virol.
74: 6592-6599
[Abstract]
[Full Text]
-
Tumpey, T. M., Lu, X., Morken, T., Zaki, S. R., Katz, J. M.
(2000). Depletion of Lymphocytes and Diminished Cytokine Production in Mice Infected with a Highly Virulent Influenza A (H5N1) Virus Isolated from Humans. J. Virol.
74: 6105-6116
[Abstract]
[Full Text]
-
Hiromoto, Y., Yamazaki, Y., Fukushima, T., Saito, T., Lindstrom, S. E., Omoe, K., Nerome, R., Lim, W., Sugita, S., Nerome, K.
(2000). Evolutionary characterization of the six internal genes of H5N1 human influenza A virus. J. Gen. Virol.
81: 1293-1303
[Abstract]
[Full Text]
-
Dybing, J. K., Schultz-Cherry, S., Swayne, D. E., Suarez, D. L., Perdue, M. L.
(2000). Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses. J. Virol.
74: 1443-1450
[Abstract]
[Full Text]
-
Kato, A., Kiyotani, K., Hasan, M. K., Shioda, T., Sakai, Y., Yoshida, T., Nagai, Y.
(1999). Sendai Virus Gene Start Signals Are Not Equivalent in Reinitiation Capacity: Moderation at the Fusion Protein Gene. J. Virol.
73: 9237-9246
[Abstract]
[Full Text]
-
Brown, E. G., Liu, H., Kit, L. C., Baird, S., Nesrallah, M.
(2001). Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes. Proc. Natl. Acad. Sci. USA
98: 6883-6888
[Abstract]
[Full Text]
-
Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. A., Cook, D. I.
(2000). From the Cover: Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia. Proc. Natl. Acad. Sci. USA
97: 10282-10287
[Abstract]
[Full Text]