SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations.

IF 5.5 2区 医学 Q1 VIROLOGY Virus Evolution Pub Date : 2023-12-28 eCollection Date: 2024-01-01 DOI:10.1093/ve/vead075
Gila Lustig, Yashica Ganga, Hylton E Rodel, Houriiyah Tegally, Afrah Khairallah, Laurelle Jackson, Sandile Cele, Khadija Khan, Zesuliwe Jule, Kajal Reedoy, Farina Karim, Mallory Bernstein, Thumbi Ndung'u, Mahomed-Yunus S Moosa, Derseree Archary, Tulio de Oliveira, Richard Lessells, Richard A Neher, Salim S Abdool Karim, Alex Sigal
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Abstract

One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with the second sub-lineage replacing the first sub-lineage in a seeming evolutionary sweep. Each sub-lineage independently evolved escape from neutralizing antibodies. The most evolved virus for the first sub-lineage (isolated day 34) and the second sub-lineage (isolated day 190) showed similar escape from ancestral SARS-CoV-2 and Delta-variant infection elicited neutralizing immunity despite having no spike mutations in common relative to the B.1 lineage. The day 190 isolate also evolved higher cell-cell fusion and faster viral replication and caused more cell death relative to virus isolated soon after diagnosis, though cell death was similar to day 34 first sub-lineage virus. These data show that SARS-CoV-2 strains in prolonged infection in a single individual can follow independent evolutionary trajectories which lead to neutralization escape and other changes in viral properties.

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在免疫抑制条件下感染 SARS-CoV-2 会形成亚系,这些亚系会独立积累中和逃逸突变。
变体形成的机制之一可能是免疫抑制人群长期感染期间的进化。为了了解在这种感染过程中进化出的病毒表型,我们对一名晚期艾滋病免疫抑制患者诊断后持续 190 多天的祖先 B.1 系感染进化出的 SARS-CoV-2 病毒进行了检测。序列和系统进化分析表明有两个不断进化的亚系,第二个亚系似乎在进化过程中取代了第一个亚系。每个亚系都独立进化出了逃避中和抗体的能力。第一个亚系(第 34 天分离)和第二个亚系(第 190 天分离)中进化程度最高的病毒表现出了类似的逃避祖先 SARS-CoV-2 的能力,尽管与 B.1 亚系相比没有共同的尖峰突变,但 Delta 变种感染可引起中和免疫。与确诊后不久分离出的病毒相比,第 190 天分离出的病毒还具有更高的细胞融合率和更快的病毒复制速度,并造成更多的细胞死亡,尽管细胞死亡与第 34 天第一亚系病毒相似。这些数据表明,SARS-CoV-2 株系在单个个体长期感染的情况下,可以遵循独立的进化轨迹,从而导致中和逃逸和病毒特性的其他变化。
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来源期刊
Virus Evolution
Virus Evolution Immunology and Microbiology-Microbiology
CiteScore
10.50
自引率
5.70%
发文量
108
审稿时长
14 weeks
期刊介绍: Virus Evolution is a new Open Access journal focusing on the long-term evolution of viruses, viruses as a model system for studying evolutionary processes, viral molecular epidemiology and environmental virology. The aim of the journal is to provide a forum for original research papers, reviews, commentaries and a venue for in-depth discussion on the topics relevant to virus evolution.
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