Lustig Gila, Ganga Yashica, Rodel Hylton, Tegally Houriiyah, Jackson Laurelle, Cele Sandile, Khan Khadija, Jule Zesuliwe, Reedoy Kajal, Karim Farina, Bernstein Mallory, Moosa Mahomed-Yunus S, Archary Derseree, de Oliveira Tulio, Lessells Richard, Abdool Karim Salim S, Sigal Alex
Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
Africa Health Research Institute, Durban, South Africa.
medRxiv. 2022 Nov 30:2022.11.23.22282673. doi: 10.1101/2022.11.23.22282673.
The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death were reduced in Omicron BA.1 infection relative to ancestral virus. Evolved virus was isolated at different times during a 6-month infection in an immunosuppressed individual with advanced HIV disease. The virus isolated 16 days post-reported symptom onset induced fusogenicity and cell death at levels similar to BA.1. However, fusogenicity was increased in virus isolated at 6 months post-symptoms to levels intermediate between BA.1 and ancestral SARS-CoV-2. Similarly, infected cell death showed a graded increase from earlier to later isolates. These results may indicate that, at least by the cellular measures used here, evolution in long-term infection does not necessarily attenuate the virus.
与奥密克戎之前的新冠病毒相比，奥密克戎感染的临床表现较轻，这增加了广泛进化导致致病性降低的可能性。为了验证这一假设，我们对长期感染过程中从原始病毒进化而来的新冠病毒诱导细胞融合和细胞死亡的情况进行了量化。与原始病毒相比，奥密克戎BA.1感染中细胞融合和死亡均减少。在一名患有晚期艾滋病的免疫抑制个体的6个月感染期间，在不同时间分离出进化病毒。报告症状出现后16天分离出的病毒诱导融合性和细胞死亡的水平与BA.1相似。然而，症状出现后6个月分离出的病毒的融合性增加到介于BA.1和原始新冠病毒之间的水平。同样，受感染细胞死亡从早期到晚期分离株呈逐渐增加趋势。这些结果可能表明，至少就此处所采用的细胞检测方法而言，长期感染中的进化不一定会使病毒减弱。
