Death Lurking in Frame

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Science  07 Dec 2001:
Vol. 294, Issue 5549, pp. 2055
DOI: 10.1126/science.294.5549.2055a

Influenza virus A has eight antisense RNA gene segments that encode 10 proteins, each of which contributes to distinct pathology in different animal hosts. Although the genome was sequenced 20 years ago, Chen et al. have serendipitously discovered a flu virus protein encoded by an open reading frame (PB1-F2) that is camouflaged within an alternative reading frame of one of the polymerase subunit genes. This open reading frame can be observed in many virus isolates from many hosts, but it is unusual in not being essential for viral replication. Furthermore, it appears to contribute to pathogenicity by promoting the death of immune cells; the PB1-F2 protein localizes to mitochondria and induces morphological changes similar to those seen in apoptotic cells. In human infections with the pandemic H2N2 and H3N2 strains of influenza virus, PB1 was one of the few segments to originate from avian viruses, and the massive loss of immune cells is associated with avian influenza.—CA

Nature Med.7, 1306 (2001).

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