Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity.

Virology. 2010 Mar 6;

Authors: Leung BW, Chen H, Brownlee GG

The influenza RNA polymerase is known to be important in pathogenicity and adaptation of avian influenza viruses to mammalian hosts. However, the molecular mechanisms responsible are only partly understood. Here we investigated the role of the polymerase in two different, closely related, H5N1 influenza viruses - a high pathogenic, A/duck/Fujian/01/2002 (FJ) strain and a low pathogenic, A/duck/Guangxi/53/2002 (GX) strain. The polymerase activity of the FJ strain was significantly greater than the GX strain. Experiments with hybrid polymerase constructs - both in vitro and in ribonucleoprotein cell-based assays, suggested that the PA and to a lesser extent the PB2 subunits of the polymerase, were responsible for increased polymerase activity of the high pathogenic strain. However, promoter binding was inversely correlated with polymerase activity implying that excessive promoter binding inhibited polymerase activity by preventing promoter clearance. Overall, we suggest that the influenza polymerase is one of the determinants of pathogenicity of duck H5N1 viruses.

PMID: 20211480 [PubMed - as supplied by publisher]

Avian Influenza A(H5N1) Viruses Can Directly Infect and Replicate in Human Gut Tissues.

J Infect Dis. 2010 Mar 8;

Authors: Shu Y, Li CK, Li Z, Gao R, Liang Q, Zhang Y, Dong L, Zhou J, Dong J, Wang D, Wen L, Wang M, Bai T, Li D, Dong X, Yu H, Yang W, Wang Y, Feng Z, McMichael AJ, Xu XN

The human respiratory tract is a major site of avian influenza A(H5N1) infection. However, many humans infected with H5N1 present with gastrointestinal tract symptoms, suggesting that this may also be a target for the virus. In this study, we demonstrated that the human gut expresses abundant avian H5N1 receptors, is readily infected ex vivo by the H5N1 virus, and produces infectious viral particles in organ culture. An autopsy colonic sample from an H5N1-infected patient showed evidence of viral antigen expression in the gut epithelium. Our results provide the first evidence, to our knowledge, that H5N1 can directly target human gut tissues.

PMID: 20210629 [PubMed - as supplied by publisher]