Restricted Infectivity of a Human-Lineage H3N2 Influenza A Virus in Pigs Is Hemagglutinin and Neuraminidase Gene Dependent

Abstract

Influenza A viruses cause pandemics at sporadic intervals. Pandemic viruses can potentially be introduced into the human population through in toto transfer of an avian influenza virus or through reassortment between avian and human strains. Pigs are believed to play a central role in the creation of pandemic viruses through reassortment because of their susceptibility to infection with both avian and human influenza viruses. However, we recently found that a human-lineage H3N2 influenza virus was highly restricted in its ability to infect pigs after intranasal inoculation. We hypothesized that this restricted infectivity phenotype was controlled by the hemagglutinin (HA) and neuraminidase (NA). To test this, we infected pigs with reverse genetics-created HA plus NA reassortant viruses. Specifically, introduction of the HA and NA genes of a contemporary H3N2 swine virus into the genetic background of the wholly human virus resulted in a significant increase in virus shedding and pathogenicity. These data indicate that the HA/NA can play important roles in controlling human influenza virus infectivity in pigs. The results further support the premise that a barrier exists to human influenza virus infection in pigs, which may limit the role of pigs in pandemic virus creation through reassortment of human and avian influenza viruses.

The Magnitude of Local Immunity in the Lungs of Mice Induced by Live Attenuated Influenza Vaccines Is Determined by Local Viral Replication and Induction of Cytokines

“…Another H3N2 wt virus, A/Wyoming/2/ 2003, also failed to replicate in the lungs of mice and was poorly pathogenic (MLD 50 of Ͼ10 6 PFU) (8) while a reassortant virus with the HA and NA genes from A/Thailand/16/2004 (H5N1) was able to replicate to high titer (8). A similar observation was reported in pigs by Landolt et al; a human H3N2 virus caused mild pulmonary lesions in pigs while a reassortant virus that possessed HA and NA genes from a swine H3N2 virus was significantly more pathogenic (29). The fact that the Panama99 (H3N2) wt virus replicates efficiently at 37°C in vitro makes it unlikely that the virus is unstable in the lungs.…”

PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs

“…In the present study, single-gene reassortant virus clones deriving the PB2 gene from Sw/Hokkaido/81 (H1N1) were isolated. It could be due to differences in the gene constellations of nonreplicating influenza virus strains bearing different host range determinants (28,49), as used by Kida et al (25) and in the present study.…”

Differentiated swine airway epithelial cell cultures for the investigation of influenza A virus infection and replication

“…Sw/MN was infectious at lower doses, exhibited more rapid and more extensive nasal shedding and caused more severe lung lesions than Sw/ONT 10 . Using reverse genetics(rg)‐created viruses in which we exchanged the hemagglutinin (HA) and neuraminidase (NA) genes between Sw/MN and Sw/ONT, we previously found that the infectivity and replication phenotypes of rgMN and rgONT in vivo are dependent on the HA and/or NA genes 11 . We subsequently examined the infection of these viruses in relatively undifferentiated monolayers of primary swine respiratory epithelial cells (SRECs) grown submerged in media in vitro .…”