Epidemiology and Evolution of Rotaviruses and Noroviruses from an Archival WHO Global Study in Children (1976–79) with Implications for Vaccine Design

Prompted by the discovery of new gastrointestinal viruses, the NIH, NIAID and WHO investigated the etiology of acute diarrhea that occurred from 1976–1979 in a global cohort of infants and young children. Rotaviruses were found to be major pathogens worldwide, whereas the Norwalk virus could not be detected using a radioimmunoassay. The aim of this study is to re-evaluate the role and diversity of rotaviruses and noroviruses in the original cohort using more sensitive current technologies. Stools collected from Asia, Africa, and South America (n = 485) were evaluated for viral genotypes by RT-PCR and sequencing. Rotaviruses were detected in 28.9% and noroviruses in 9.7% of the specimens, with G1 rotaviruses and GII noroviruses accounting for the majority of each respective virus. Various strains in this study predated the currently assigned dates of discovery for their particular genotype, and in addition, two noroviruses (KL45 and T091) could not be assigned to current genotypes. Phylogenetic analyses demonstrated a relative constancy in circulating rotavirus genotypes over time, with several genotypes from this study becoming established in the current repertoire of viral species. Similarly, GII noroviruses have maintained dominance, with GII.4 noroviruses continuing as a predominant genotype over time. Taken together, the complex molecular epidemiology of rotaviruses and noroviruses circulating in the 1970’s is consistent with current patterns, an important consideration in the design of multivalent vaccines to control these viruses.鉴于新型胃肠道病毒的发现，美国国立卫生研究院（National Institutes of Health, NIH）、美国国家过敏和传染病研究所（National Institute of Allergy and Infectious Diseases, NIAID）与世界卫生组织（World Health Organization, WHO）针对1976年至1979年全球婴幼儿队列中发生的急性腹泻开展了病因学调查。研究发现轮状病毒（Rotavirus）是全球范围内的主要致病原，而采用放射免疫测定法无法检出诺沃克病毒（Norwalk virus）。本研究旨在利用当前更为灵敏的技术，重新评估上述原始队列中轮状病毒与诺如病毒的致病作用及多样性。研究人员通过逆转录聚合酶链式反应（Reverse Transcription-Polymerase Chain Reaction, RT-PCR）与测序技术，对取自亚洲、非洲及南美洲的485份粪便样本进行病毒基因型检测。结果显示，样本中轮状病毒检出率为28.9%，诺如病毒为9.7%；其中G1型轮状病毒与GII型诺如病毒分别为两类病毒的优势株。本研究中的多株病毒早于当前对应基因型的公认发现时间，此外，两株诺如病毒（KL45与T091）无法归类至现有基因型。系统发育分析表明，随时间推移，循环流行的轮状病毒基因型相对稳定，本研究中的部分基因型现已纳入当前病毒物种名录。类似地，GII型诺如病毒始终占据优势地位，其中GII.4型诺如病毒长期以来均为优势基因型。综合来看，1970年代流行的轮状病毒与诺如病毒的复杂分子流行病学特征与当前流行模式一致，这为防控此类病毒的多价疫苗研发提供了重要参考依据。