The D. I. Ivanovsky Institute of Virology, Gamaleya Str. 16, Moscow 123098, Russia1
St Jude Childrens Research Hospital, Department of Virology and Molecular Biology, 332 N. Lauderdale, Memphis, Tennessee 38105, USA2
Avian Viruses Section, Diagnostic Virology Laboratory, National Veterinary Service Laboratories, APHIS, United States Department of Agriculture, PO Box 844, Ames, Iowa 50010, USA3
Author for correspondence: Natalia Makarova (at The D. I. Ivanovsky Institute of Virology). Fax +7 095 5165314. e-mail finmed{at}glasnet.ru
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() |
---|
![]() |
Main text |
---|
![]() ![]() ![]() ![]() |
---|
Influenza viruses of the H2 subtype circulated in the human population until 1968, after which they continued to be detected in avian populations (Tumova et al., 1975 ; Shortridge, 1979
; Sinnecker et al., 1983
; Wright et al., 1992
). Most H2N2 viruses in wild and domestic birds are antigenically closely related to the viruses that circulated in the human population between 1957 and 1968, suggesting that viruses similar to the progenitor of the Asian/57 pandemic are still circulating in birds (Schafer et al., 1993
). Serological data showed that the percentage of detection of anti-H2 antibodies in the sera of adults was low, and no anti-H2 antibodies were detected in the sera of children (Govorkova et al., 1993
). These facts emphasize the importance of periodical surveillance of avian H2 influenza viruses and elucidation of the phylogenetic and evolutionary relationships among present and previously known avian H2 influenza viruses.
The two distinct lineages of avian H2 influenza viruses, American and Eurasian, are distinguished by their geographical origins (Schafer et al., 1993 ). One virus isolated in the USA, A/Herring gull/Delaware/677/88, has been shown to belong to the Eurasian lineage, but that single observation could not be conclusively interpreted. To elucidate the evolutionary characteristics of recently isolated avian viruses of the H2 subtype, we investigated the antigenic and phylogenetic relationships among recent and previously described avian influenza H2 viruses.
The viruses used in these studies (Table 1) were obtained as part of surveillance programs in the northeastern part of the USA and in Alberta, Canada, or from the virus repository at St Jude Childrens Research Hospital, Memphis, TN, USA. The shorebird and gull viruses were isolated from samples collected annually in mid-May from the Delmarva Peninsula region of the USA between 1985 and 1998 (Kawaoka et al., 1988
). Influenza viruses from migratory ducks were isolated between 1977 and 1997 from samples collected annually in late July to early September in Alberta, Canada (Sharp et al., 1993
). Viruses were propagated at low m.o.i. in the allantoic cavity of 11-day-old embryonated chicken eggs.
|
The phylogenetic tree (Fig. 1) confirms the divergence of H2 influenza A viruses into two distinct geographical lineages: American and Eurasian. All newly sequenced HA1 genes from domestic poultry were of the American lineage. However, a large group of recent American isolates from shorebirds in Delaware Bay belonged to the Eurasian lineage. As reported previously (Schafer et al., 1993
), the A/Herring gull/Delaware/677/88 strain isolated in Delaware Bay also is of the Eurasian lineage. Together, the viruses isolated in Delaware Bay composed a divergent sublineage in the Eurasian section of the tree. All of these viruses were isolated from seabirds (gulls and shorebirds). Interestingly, two viruses previously isolated from gulls in North America (A/Gull/Maryland/19/77 and A/Laughing gull/New Jersey/75/85) were of the American lineage but diverged from other isolates of that lineage. A/Peking duck/Potsdam/1689-4/85 was the Eurasian virus most closely related to the group of American viruses with Eurasian HA. These data suggest that Eurasian H2 was transmitted from Eurasian to American avian hosts.
|
As shown previously, human influenza viruses evolve rapidly because of the pressure of the neutralizing antibodies of the host (Both et al., 1983 ). Avian species produce humoral and cell-mediated responses to influenza virus infection, but their antibody responses are short-lived (Kida et al., 1980
); moreover, a large number of young susceptible birds are produced every year, eliminating the immune pressure among avian viruses. The high rate of HA evolution in Eurasian-type American H2 viruses suggests the existence of an unknown positive selection mechanism that favours amino acid changes in the transferred virus, probably connected with the transfer to the new environment. This finding is also at variance with our earlier findings of evolutionary stasis among influenza viruses in their natural reservoirs (Webster et al., 1992
) and indicates that this may not apply to all aquatic birds.
The higher percentage of amino acid replacements in the HA of the Delaware group of viruses may lead to changes in their antigenic reactivity pattern. To investigate this possibility, haemagglutination titrations and haemagglutination inhibition (HI) assays were performed as previously described (Rogers et al., 1983 ). Ascitic fluids from mice containing monoclonal antibodies (MAbs) to the HA of the H2 influenza subtype (Yamada et al., 1984
) were used in the HI tests. The HA of avian viruses isolated in North America demonstrated two patterns of reactivity with the panel of MAbs (Table 2
). However, the antigenic and phylogenetic groups did not coincide. The American viruses react with most MAbs in the panel. In contrast, the Delaware Bay (shorebird and gull) viruses reacted with only two or three MAbs. This pattern of reactivity, which had been reported earlier for one Delaware Bay shorebird strain (A/Herring gull/Delaware/677/88), extended to all of the four shorebird viruses characterized. However, the Delaware Bay strains are not unique in this respect. One Eurasian strain, A/Duck/GDR/72, and one American strain, A/Chicken/New York/29878/91, had shown a similar pattern of reaction (Schafer et al., 1993
).
|
Several influenza A virus HA subtypes comprise geographically separate lineages (Garcia et al., 1997 ; Donis et al., 1989
). These lineages may have emerged because of nonoverlapping migration routes. Most wild birds follow NorthSouth migration routes that are separate for each hemisphere. Further, the birds that migrate across the Atlantic do so at times when NorthSouth migrations are over. For example, the Canadian terns and gulls that cross the Atlantic (Curry-Lindahl, 1975
) arrive in Europe after the European birds have migrated to Africa. On rare occasions, unusual weather conditions may bring the two populations into contact, allowing the interregional transmission of viruses. Turnstones, which are pelagic birds and whose migration is not fully resolved, may play a role in this transmission (Curry-Lindahl, 1975
). However, such occasional transmissions would be unlikely to lead in each case to circulation of the transferred virus; otherwise, the phylogenetically distinct lineages would not have arisen. The circulation of Eurasian H2 virus in the Delaware shorebirds for at least 10 years does not necessarily suggest the existence of some specific, as yet unknown, conditions in the area that favour the virus: new Eurasian-type H2 viruses may be circulating in other parts of America as well. All of the sequenced H2 viruses isolated from gulls in other parts of America were isolated earlier than 1988. The first Delaware Eurasian-type virus was isolated in 1988. If the transfer occurred not long before 1988, it is possible that the Eurasian-type viruses are in fact not restricted to Delaware Bay but are instead restricted to shorebirds and gulls (Kawaoka et al., 1988
).
H2 virus is the only pandemic influenza virus subtype that has not circulated in the human population for the last 30 years. Therefore, the probability that H2 viruses will reappear in humans may be high. It is generally accepted that the 1957 and 1968 influenza pandemics were produced by reassortant human strains with HA genes that originated from avian influenza viruses. Although the details of the transfer of Eurasian H2 virus strains to North America are not yet clear, the existence of this transfer has important implications. The Eurasian avian influenza virus strains are those most closely related to human H2 viruses (Schafer et al., 1993 ) and are potential sources of genes for future pandemic influenza strains. These are compelling reasons for the further study and surveillance of avian H2 strains circulating in the Americas.
![]() |
Acknowledgments |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() |
---|
Both, G. W., Sleigh, M. J., Cox, N. J. & Kendal, A. P. (1983). Antigenic drift in influenza virus H3 hemagglutinin from 1968 to 1980: multiple evolutionary pathways and sequential amino acid changes at key antigenic sites. Journal of Virology 48, 52-60.[Medline]
Curry-Lindahl, K. (1975). Faglar over land och hav. En global oversikt av faglarnas flyttning, pp. 113114. Stockholm: Albert Bonniers Forlag.
Donis, R. O., Bean, W. J., Kawaoka, Y. & Webster, R. G. (1989). Distinct lineages of influenza virus H4 hemagglutinin genes in different regions of the world. Virology 169, 408-417.[Medline]
Fitch, W. M. (1970). Distinguishing homologous from analogous proteins. Systematic Zoology 19, 99-113.[Medline]
Garcia, M., Suarez, D. L., Crawford, J. M., Latimer, J. W., Slemons, R. D., Swayne, D. E. & Perdue, M. L. (1997). Evolution of H5 subtype avian influenza A viruses in North America. Virus Research 51, 115-124.[Medline]
Govorkova, E. A., Kizina, A. A., Krylov, V. F. & Smirnov, I. (1993). The level of population immunity to influenza A viruses with haemagglutinin subtype H2. Zhurnal Mikrobiologii Epidemiologii i Immunobiologii 6, 5859 (in Russian).
Huddleston, J. A. & Brownlee, G. G. (1982). The sequence of the nucleoprotein gene of human influenza A virus, strain A/NT/60/68. Nucleic Acids Research 10, 1029-1038.[Abstract]
Kawaoka, Y., Chambers, T. M., Sladen, W. L. & Webster, R. G. (1988). Is the gene pool of influenza viruses in shorebirds and gulls different from that in wild ducks? Virology 163, 247-250.[Medline]
Kawaoka, Y., Krauss, S. & Webster, R. G. (1989). Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. Journal of Virology 63, 4603-4608.[Medline]
Kida, H., Yanagawa, R. & Matsuoka, Y. (1980). Duck influenza lacking evidence of disease signs and immune response. Infection and Immunity 30, 547-553.[Medline]
Mulder, J. & Masurel, N. (1958). Pre-epidemic antibody against 1957 strain of Asiatic influenza in serum of older people living in the Netherlands. Lancet i, 810814.
Nobusawa, E., Aoyama, T., Kato, H., Suzuki, Y., Tateno, Y. & Nakajima, K. (1991). Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses. Virology 182, 475-485.[Medline]
Rogers, G. N., Pritchett, T. J., Lane, J. L. & Paulson, J. C. (1983). Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants. Virology 131, 394-408.[Medline]
Saitou, N. & Nei, M. (1987). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4, 406-425.[Abstract]
Schafer, J. R., Kawaoka, Y., Bean, W. J., Suss, J., Senne, D. & Webster, R. G. (1993). Origin of the pandemic 1957 H2 influenza A virus and the persistence of its possible progenitors in the avian reservoir. Virology 194, 781-788.[Medline]
Scholtissek, C., Rohde, W., Von Hoyningen, V. & Rott, R. (1978). On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 87, 13-20.[Medline]
Sharp, G. B., Kawaoka, Y., Wright, S. M., Turner, B., Hinshaw, V. & Webster, R. G. (1993). Wild ducks are the reservoir for only a limited number of influenza A subtypes. Epidemiology and Infection 110, 161-176.[Medline]
Shortridge, K. F. (1979). H2N2 influenza viruses in domestic ducks [letter]. Lancet i, 439.
Sinnecker, R., Sinnecker, H., Zilske, E. & Kohler, D. (1983). Surveillance of pelagic birds for influenza A viruses. Acta Virologica 27, 75-79.[Medline]
Tumova, B., Eisengarten, H. J., Siebelist-Konstantinow, I., Stumpa, A. & Webster, R. G. (1975). A duck influenza virus with haemagglutinin related to that of A/Singapore/57 (H2N2) virus. Acta Virologica 19, 261.[Medline]
Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. (1992). Evolution and ecology of influenza A viruses. Microbiological Reviews 56, 152-179.[Abstract]
Wiley, D. C., Wilson, I. A. & Skehel, J. J. (1981). Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373-378.[Medline]
Wright, S. M., Kawaoka, Y., Sharp, G. B., Senne, D. A. & Webster, R. G. (1992). Interspecies transmission and reassortment of influenza A viruses in pigs and turkeys in the United States. American Journal of Epidemiology 136, 488-497.[Abstract]
Yamada, A., Brown, L. E. & Webster, R. G. (1984). Characterization of H2 influenza virus hemagglutinin with monoclonal antibodies: influence of receptor specificity. Virology 138, 276-286.[Medline]
Received 13 May 1999;
accepted 13 August 1999.