專題討論14:季節流感與H1N1新流感

S14-1
季節流感及新型流感病毒學
The Virology of Seasonal Influenza and 2009 Pandemic Influenza A (H1N1)
Jhe-Ming Chen2 (陳哲明) and Jen-Ren Wang1,2* (王貞仁)
Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University1; NHRI Tainan Virology Laboratory for Diagnosis and Research, Division of Infectious Diseases, National Health Research Institutes 2

  In April 2009, a novel influenza strain (swine-origin influenza virus A (H1N1), pandemic influenza A (H1N1), 2009 A(H1N1) influenza virus) which crossed the species barrier, was first identified in Mexico and continued to cause outbreaks globally. On June 11, the WHO declared an H1N1 pandemic, moving the alert level to phase 6. The pandemic Influenza A (H1N1) is a quadruple reassortant and mixed genetic elements through swine as intermediate host. The genetic elements were originated from four different influenza viruses: North American swine influenza (H1, NP, NS), North American avian influenza (PB2, PA), human influenza H3N2 (PB1), and Eurasian swine influenza (N1, M). The 2009 A(H1N1) influenza viruses, although a zoonotic influenza virus, exhibited sustained human-to-human transmission. The protein sequence divergence of this 2009 A(H1N1) virus from human seasonal influenza H1 is about 20%. To date 2009 A(H1N1) influenza viruses exhibit high genome sequence identity (99.9%) and lack previously identified molecular markers of influenza A virus virulence or transmissibility. The genome of influenza virus consists of eight negative strand RNA segments that each encodes one or two proteins. The hemagglutinin (HA) protein has an important role for binding to receptors and HA cleavage is essential for viral infectivity. Replications and transcription of viral RNAs are carried out by three polymerase subunits (PB2, PB1, PA), and the nucleoprotein NP. Newly synthesized viral ribonucleoprotein complexes are exported from the nucleus by the nuclear export protein and the matrix protein M1. The neuraminidase NA protein facilitates virus release from the infected cells and the M2 protein functions as an ion channel. In addition, the NS1 protein acts as host interferon antagonist and PB1-F2 protein has been previously associated with the increased pathogenicity of the 1918 virus and highly pathogenic H5N1 virus. Unlike seasonal flu, 2009 A(H1N1) influenza viruses can infect cells deep in the lung. Seasonal flu could only infect cells with α2,6-galactose-linked sialic acid receptors which are typically located in the nose and throat, but 2009 A(H1N1) influenza viruses can also infect cells with receptor type α2-3. Influenza virus pathogenicity is multigenic, and the determinants of pathogenicity may differ among animal species. The determinants of viral pathogenicity will be further discussed.