Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
J Virol. 2011 Jan;85(1):231-42. doi: 10.1128/JVI.01364-10. Epub 2010 Oct 27.
Noroviruses are the principal cause of epidemic gastroenteritis worldwide. Multiple reports have concluded that the major capsid proteins of GII.4 strains, which cause 80% of norovirus infections worldwide, are evolving rapidly, resulting in new epidemic strains. Surrogate neutralization assays using sera from outbreaks and from immunized mice suggest that, as with influenza virus, antigenic variation maintains GII.4 persistence in the face of human population herd immunity. To test this hypothesis, mice were hyperimmunized with virus-like particles (VLPs) representing an early (GII.4-1987) and a contemporary (GII.4-2006) GII.4 strain. Anti-GII.4-1987 IgG monoclonal antibodies (MAbs) strongly reacted with GII.4 VLPs derived between only 1987 and 2002. Ligand binding blockade was more efficient with GII.4-1987 and GII.4-1997 VLPs than with GII.4-2002. Anti-GII.4-2006 IgG MAbs recognized either a broad panel of GII.4 VLPs (1987 to 2006) or a subset of contemporary (2004 to 2006) VLPs. Most 2006 antibodies did not recognize or only poorly recognized GII.4 VLPs of 2007 or 2008, documenting rapid antigenic evolution of GII.4 capsids. Generally, 2006 MAbs blocked homotypic VLP-ligand binding but were unable to block VLPs representing strains primarily circulating during or earlier than 2002. These analyses demonstrate that both subtle and significant evolutionary change has occurred within antibody epitopes between epidemic strains, providing direct evidence that the GII.4 noroviruses are undergoing antigenic variation, likely in response to herd immunity. As with influenza virus, HIV, and hepatitis C virus, norovirus antigenic variation will significantly influence the design of efficacious vaccines and immunotherapeutics against these important human pathogens.
诺如病毒是全球范围内引起流行性肠胃炎的主要原因。多项报告的结论表明，引起全球 80%诺如病毒感染的 GII.4 株的主要衣壳蛋白正在迅速进化，导致新的流行株出现。使用暴发和免疫小鼠的血清进行替代中和测定表明，与流感病毒一样，抗原变异使 GII.4 在面对人群群体免疫时得以持续存在。为了验证这一假说，用代表早期（GII.4-1987）和当代（GII.4-2006）GII.4 株的病毒样颗粒（VLPs）对小鼠进行超免疫接种。抗 GII.4-1987 IgG 单克隆抗体（MAb）与仅在 1987 年至 2002 年之间衍生的 GII.4 VLP 强烈反应。与 GII.4-2002 相比，GII.4-1987 和 GII.4-1997 VLP 的配体结合阻断更为有效。抗 GII.4-2006 IgG MAb 识别广泛的 GII.4 VLP 组（1987 年至 2006 年）或当代（2004 年至 2006 年）VLP 的子集。大多数 2006 年抗体不识别或仅轻度识别 2007 年或 2008 年的 GII.4 VLP，证明 GII.4 衣壳的抗原快速进化。通常，2006 MAb 阻断同种型 VLP-配体结合，但无法阻断主要在 2002 年或之前循环的菌株代表的 VLP。这些分析表明，在流行株之间的抗体表位中已经发生了细微和显著的进化变化，这直接证明 GII.4 诺如病毒正在发生抗原变异，可能是对群体免疫的反应。与流感病毒、艾滋病毒和丙型肝炎病毒一样，诺如病毒的抗原变异将极大地影响针对这些重要人类病原体的有效疫苗和免疫疗法的设计。
