Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques
Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques
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DOI：
10.1128/jvi.03030-12
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
--
作者：
Jegaskanda, Sinthujan;Weinfurter, Jason T.;Kent, Stephen J.
新出现的流感病毒对全球人类健康构成严重威胁。最近对雪貂、猕猴和人类的研究表明，季节性H1N1（sH 1 N1）感染对2009年大流行性流感病毒（H1N1 pdm）提供了一些交叉保护，但对交叉保护的相关性知之甚少。在这里，我们表明，季节性感染流感病毒的印度恒河猴（猕猴）与A/川崎/173/2001（sH 1 N1）病毒诱导的抗体能够结合血凝素（HA）的同源季节性病毒和抗原分歧A/加州/04/2009（H1N1 pdm）株在没有可检测的H1N1 pdm特异性中和抗体。这些流感病毒特异性抗体激活猕猴NK细胞，在来自sH 1 N1或H1N1 pdm病毒的HA蛋白存在下表达CD 107 a和γ干扰素（IFN-γ）。虽然流感病毒特异性抗体依赖性细胞毒性（ADCC）介导的NK细胞激活随着时间的推移减少滴度sH 1 N1感染后，这些细胞迅速扩大后7天内H1N1 pdm曝光。此外，我们发现流感病毒特异性ADCC存在于支气管肺泡灌洗液中，并且能够激活肺NK细胞。我们的结论是，感染季节性流感病毒可以诱导抗体介导ADCC能够识别不同的流感病毒株。交叉反应性ADCC可能提供了一种降低不同流感病毒感染严重程度的机制。
Emerging influenza viruses pose a serious risk to global human health. Recent studies in ferrets, macaques, and humans suggest that seasonal H1N1 (sH1N1) infection provides some cross-protection against 2009 pandemic influenza viruses (H1N1pdm), but the correlates of cross-protection are poorly understood. Here we show that seasonal infection of influenza-naive Indian rhesus macaques (Macaca mulatta) with A/Kawasaki/173/2001 (sH1N1) virus induces antibodies capable of binding the hemagglutinin (HA) of both the homologous seasonal virus and the antigenically divergent A/California/04/2009 (H1N1pdm) strain in the absence of detectable H1N1pdm-specific neutralizing antibodies. These influenza virus-specific antibodies activated macaque NK cells to express both CD107a and gamma interferon (IFN-gamma) in the presence of HA proteins from either sH1N1 or H1N1pdm viruses. Although influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-mediated NK cell activation diminished in titer over time following sH1N1 infection, these cells expanded rapidly within 7 days following H1N1pdm exposure. Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.