Emergence and pandemic potential of swine-origin H1N1 influenza virus

Abstract

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.

Fig. 1. Schematic diagram of influenza A viruses

Virions are decorated with two surface glycoproteins, HA and NA. The genome is composed of eight segments of single-stranded RNA that interact with the nucleoprotein and the components of polymerase complex (PB2, PB1, PA).

Fig. 2. Schematic diagram of the influenza viral life cycle

Following receptor-mediated endocytosis, the viral ribonucleoprotein (vRNP) complexes are released into the cytoplasm and subsequently transported to the nucleus, where replication and transcription take place. mRNAs are exported to the cytoplasm for translation. Early viral proteins, i.e., those required for replication and transcription, are transported back to the nucleus. Late in the infection cycle, the M1 and NS2(=NEP) proteins facilitate the nuclear export of newly synthesized vRNPs. PB1-F2 associates with mitochondria. The assembly and budding of progeny virions occurs at the plasma membrane.

Fig. 3. Emergence of pandemic influenza viruses

The ‘Spanish influenza’ was most likely caused by the transmission of an avian influenza virus to humans. In 1957, the introduction of avian virus H2 HA, N2 NA, and PB1 genes into human populations resulted in the ‘Asian influenza’. Similarly, the introduction of avian virus H3 HA and PB1 genes into human populations led to the ‘Hong Kong influenza’ in 1968. In 1977, H1N1 viruses reappeared which closely resembled strains that had been circulating in the mid 1950's.

Fig. 4. Genesis of swine-origin H1N1 influenza viruses

In the late 1990's, reassortment between human H3N2, North American avian, and classical swine viruses resulted in triple reassortant H3N2 and H1N2 swine viruses that have since circulated in North American pig populations. A triple reassortant swine virus reassorted with a Eurasian avian-like swine virus, resulting in the S-OIV that are now circulating in humans.

Fig. 5. Electron microscopic picture of recently emerged swine-origin H1N1 viruses

Madin-Darby canine kidney cells were infected with A/California/04/09 (H1N1) virus and observed by thin section electron microscopy 24 hours later. Most virus particles showed a filamentous shape of more than 1 μm in length. Bar, 1 μm.