Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.
Sci Rep. 2016 Dec 22;6:39505. doi: 10.1038/srep39505.
Acquisition of a polybasic cleavage site (pCS) in the hemagglutinin (HA) is a prerequisite for the shift of low pathogenic (LP) avian influenza virus (AIV) to the highly pathogenic (HP) form in chickens. Whereas presence of a pCS is required for high pathogenicity, less is known about the effect of composition of pCS on virulence of AIV particularly H7N7. Here, we investigated the virulence of four avian H7N7 viruses after insertion of different naturally occurring pCS from two HPAIV H7N7 (designated pCSGE and pCSUK) or from H7N1 (pCSIT). In vitro, the different pCS motifs modulated viral replication and the HA cleavability independent on the HA background. However, in vivo, the level of virulence conferred by the different pCS varied significantly. Within the respective viral backgrounds viruses with pCSIT and pCSGE were more virulent than those coding for pCSUK. The latter showed also the most restricted spread in inoculated birds. Besides the pCS, other gene segments modulated virulence of these H7N7 viruses. Together, the specific composition of the pCS significantly influences virulence of H7N7 viruses. Eurasian LPAIV H7N7 may shift to high pathogenicity after acquisition of "specific" pCS motifs and/or other gene segments from HPAIV.
获得血凝素（HA）中的多碱性裂解位点（pCS）是低致病性（LP）禽流感病毒（AIV）在鸡中向高致病性（HP）形式转变的前提。虽然存在 pCS 是高致病性所必需的，但对于 pCS 的组成对 AIV，特别是 H7N7 的毒力的影响知之甚少。在这里，我们研究了插入来自两种高致病性禽流感（HPAIV）H7N7（分别命名为 pCSGE 和 pCSUK）或 H7N1（pCSIT）的不同天然存在的 pCS 后，四种禽源 H7N7 病毒的毒力。在体外，不同的 pCS 基序独立于 HA 背景调节病毒复制和 HA 裂解性。然而，在体内，不同 pCS 赋予的毒力水平差异很大。在各自的病毒背景下，带有 pCSIT 和 pCSGE 的病毒比编码 pCSUK 的病毒更具毒力。后者在接种鸟类中的传播也受到限制。除了 pCS 外，其他基因片段也调节了这些 H7N7 病毒的毒力。总之，pCS 的特定组成显著影响 H7N7 病毒的毒力。欧亚大陆的 LPAIV H7N7 在获得 HPAIV 的“特定”pCS 基序和/或其他基因片段后可能会向高致病性转变。
