科学家可能发现了一个让甲型H1N1流感病毒从动物跳到人身上的关键分子突变之一。Andrew Mehle 和Jennifer Doudna指出,由病毒蛋白PB1、PB2和PA组成的流感病毒聚合酶通常有助于决定病毒感染宿主的难易程度。特别是PB2的一个突变(它用赖氨酸替代了谷氨酸)通常对于禽流感和猪流感感染人类是必不可少的。但是H1N1病毒并没有这个突变。这组科学家发现了H1N1 PB2的含有丝氨酸和精氨酸的亚单位的另一种突变。这个名为SR多态的突变增强了病毒聚合酶的活性以及病毒在人体细胞培养中的病毒复制,甚至把它们加入到通常不能感染人类细胞的流感病毒中也是如此。这组作者提出,这些适应可能有助于解释H1N1病毒如何传给了人,而且可能提示甲型H1N1病毒有能力发展出可能改善其在人体内的复制能力的额外突变。

http://www.bioon.com/biology/sars/423609.shtml

生物谷推荐原始出处:

PNAS December 7, 2009, doi: 10.1073/pnas.0911915106

Adaptive strategies of the influenza virus polymerase for replication in humans

Andrew Mehlea and Jennifer A. Doudnaa,b,c,1

aDepartments of Molecular and Cell Biology and
bChemistry, Howard Hughes Medical Institute, University of California, Berkeley, CA 94705; and
cPhysical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Transmission of influenza viruses into the human population requires surmounting barriers to cross-species infection. Changes in the influenza polymerase overcome one such barrier. Viruses isolated from birds generally contain polymerases with the avian-signature glutamic acid at amino acid 627 in the PB2 subunit. These polymerases display restricted activity in human cells. An adaptive change in this residue from glutamic acid to the human-signature lysine confers high levels of polymerase activity in human cells. This mutation permits escape from a species-specific restriction factor that targets polymerases from avian viruses. A 2009 swine-origin H1N1 influenza A virus recently established a pandemic infection in humans, even though the virus encodes a PB2 with the restrictive glutamic acid at amino acid 627. We show here that the 2009 H1N1 virus has acquired second-site suppressor mutations in its PB2 polymerase subunit that convey enhanced polymerase activity in human cells. Introduction of this polymorphism into the PB2 subunit of a primary avian isolate also increased polymerase activity and viral replication in human and porcine cells. An alternate adaptive strategy has also been identified, whereby introduction of a human PA subunit into an avian polymerase overcomes restriction in human cells. These data reveal a strategy used by the 2009 H1N1 influenza A virus and identify other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans