Influenza A (H5N1) Viruses from Pigs, Indonesia | CDC EID

EID Journal Home > Volume 16, Number 10–October 2010

Volume 16, Number 10–October 2010
Research
Influenza A (H5N1) Viruses from Pigs, Indonesia
Chairul A. Nidom, Ryo Takano, Shinya Yamada, Yuko Sakai-Tagawa, Syafril Daulay, Didi Aswadi, Takashi Suzuki, Yasuo Suzuki, Kyoko Shinya, Kiyoko Iwatsuki-Horimoto, Yukiko Muramoto, and Yoshihiro Kawaoka
Author affiliations: Airlangga University, Surabaya, East Java, Indonesia (C.A. Nidom); University of Tokyo, Tokyo, Japan (R. Takano, S. Yamada, Y. Sakai-Tagawa, K. Iwatsuki-Horimoto, Y. Muramoto, Y. Kawaoka); Ministry of Agriculture, Jakarta, Indonesia (S. Daulay); Agriculture and Livestock Agency, Tangerang, Indonesia (D. Aswadi); University of Shizuoka, Shizuoka City, Japan (T. Suzuki, Y. Suzuki); Chubu University, Kasugai City, Japan (Y. Suzuki); Kobe University, Kobe, Japan (K. Shinya, Y. Kawaoka); and University of Wisconsin, Madison, Wisconsin, USA (Y. Kawaoka)

Suggested citation for this article

Abstract
Pigs have long been considered potential intermediate hosts in which avian influenza viruses can adapt to humans. To determine whether this potential exists for pigs in Indonesia, we conducted surveillance during 2005–2009. We found that 52 pigs in 4 provinces were infected during 2005–2007 but not 2008–2009. Phylogenetic analysis showed that the viruses had been introduced into the pig population in Indonesia on at least 3 occasions. One isolate had acquired the ability to recognize a human-type receptor. No infected pig had influenza-like symptoms, indicating that influenza A (H5N1) viruses can replicate undetected for prolonged periods, facilitating avian virus adaptation to mammalian hosts. Our data suggest that pigs are at risk for infection during outbreaks of influenza virus A (H5N1) and can serve as intermediate hosts in which this avian virus can adapt to mammals.


A highly pathogenic avian influenza virus A (H5N1) was first recognized among geese in Guangdong Province, southern People’s Republic of China, in 1996 (1). Within a year, this goose virus underwent reassortment with viruses circulating in other avian species. By 1997, the virus had become widespread among poultry in Hong Kong, and direct avian-to-human transmission of influenza A (H5N1) viruses was reported (2,3). Since late 2003, influenza A (H5N1) viruses have spread to domestic poultry in other Southeast Asian countries (4). Since mid 2005, they have been detected across Asia, Europe, and Africa, causing severe damage to the poultry industry and infecting >490 humans, resulting in a mortality rate of 60% (5–8). Indonesia has been particularly affected by these viruses; >160 cases of human infection (i.e., about one third of the total confirmed human influenza A (H5N1) infections worldwide) and a mortality rate >80% have been reported (8). Hence, understanding prevalence and adaptation of influenza A (H5N1) influenza viruses in Indonesia is crucial.

Influenza viruses attach to host cells by binding their hemagglutinin (HA) to cell-surface oligosaccharides containing a terminal sialic acid. The HA of avian influenza viruses preferentially binds to sialic acid linked to galactose by α-2,3 linkages (SAα2,3Gal); that of human viruses binds to SAα2,6Gal (9). Correspondingly, epithelial cells in the upper respiratory tracts of humans mainly bear SAα2,6Gal receptors (10,11), and those in duck intestines (the major replication site for duck viruses) mainly possess SAα2,3Gal (12). Virus receptor specificities and expression patterns of receptors on host cells are thought to be major determinants of the host range restriction of influenza viruses (13). Thus, the recognition of human-type receptors by avian viruses appears to be necessary for these viruses to replicate in the upper respiratory tract and be transmitted efficiently from human to human. Given that influenza A (H5N1) viruses isolated from humans are not transmitted efficiently despite their ability to recognize human-type receptors (14), mutations in the polymerase and other viral genes may also be needed for replication of influenza A (H5N1) viruses in the upper respiratory tract (15).

Traditionally, pigs have been considered as “mixing vessels” (16–19) because they support replication of avian and human influenza viruses (17). Their tracheal epithelial cells reportedly bear SAα2,3Gal and SAα2,6Gal receptors (18). However, recent studies have shown that despite SAα2,3Gal and SAα2,6Gal receptors in pig respiratory tracts, SAα2,3Gal is found only in the smaller airways (bronchioli and alveoli) and not in the trachea (20,21). Kuchipudi et al. (22) found SAα2,3Gal and SAα2,6Gal receptors in the bronchi, bronchioli, and alveoli of chickens and ducks; however, SAα2,6Gal was dominant in chicken tracheal epithelium, and SAα2,3Gal, in duck trachea. Given that influenza A (H5N1) viruses have been transmitted directly from birds to humans, the central dogma of pigs as a mixing vessel may no longer stand. Moreover, under experimental conditions, pig susceptibility to infection with avian influenza A (H5N1) viruses is low (23). Nevertheless, the pandemic (H1N1) 2009 virus is a reassortant that originated from 4 genetically distinct viruses and appeared to be generated in pigs (24), suggesting their role in the generation of pandemic influenza viruses. Infection of pigs with influenza A (H5N1) viruses has been reported in Vietnam (25) and China (26); however, the infection status of pigs in Indonesia remains unknown. We, therefore, explored whether pigs in Indonesia had been infected with influenza A (H5N1) viruses and, if so, whether the viruses were transmitted multiple times and had acquired the ability to recognize human-type receptors.

full-text (large):
Influenza A (H5N1) Viruses from Pigs, Indonesia | CDC EID


Suggested Citation for this Article
Nidom CA, Takano R, Yamada S, Sakai-Tagawa Y, Daulay S, Aswadi, D, et al. Influenza A (H5N1) viruses from pigs, Indonesia. Emerg Infect Dis [serial on the Internet]. 2010 Oct [date cited]. http://www.cdc.gov/EID/content/16/10/1515.htm

DOI: 10.3201/eid1610.100508


Comments to the Authors
Please use the form below to submit correspondence to the authors or contact them at the following address:

Address for correspondence: Yoshihiro Kawaoka, Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo.108-8639, Japan; email: kawaoka@ims.u-tokyo.ac.jp