期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：27
DOI：10.1073/pnas.2122050119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
In the combined antiretroviral therapy era, lymphomas still represent the most frequent cause of death in HIV-1-infected patients. We expand previous observations dealing with the prevalence of HIV-1 matrix protein p17 variants (vp17s), characterized by peculiar amino acid insertions and endowed of B cell clonogenic activity, in HIV-1 patients with lymphoma as compared with patients without lymphoma. We show that the prevalence of HIV-1 mutants expressing vp17s is increasing worldwide over time. Moreover, we describe a cluster of HIV-1 mutants expressing a B cell clonogenic vp17 and highlight that insertions can be fixed and that viruses displaying clonogenic vp17s are actively spreading. This knowledge advocates for an extensive genomic surveillance program to monitor the evolution of such mutant virions worldwide.
AIDS-defining cancers declined after combined antiretroviral therapy (cART) introduction, but lymphomas are still elevated in HIV type 1 (HIV-1)–infected patients. In particular, non-Hodgkin’s lymphomas (NHLs) represent the majority of all AIDS-defining cancers and are the most frequent cause of death in these patients. We have recently demonstrated that amino acid (aa) insertions at the HIV-1 matrix protein p17 COOH-terminal region cause protein destabilization, leading to conformational changes. Misfolded p17 variants (vp17s) strongly impact clonogenic B cell growth properties that may contribute to B cell lymphomagenesis as suggested by the significantly higher frequency of detection of vp17s with COOH-terminal aa insertions in plasma of HIV-1–infected patients with NHL. Here, we expand our previous observations by assessing the prevalence of vp17s in large retrospective cohorts of patients with and without lymphoma. We confirm the significantly higher prevalence of vp17s in lymphoma patients than in HIV-1–infected individuals without lymphoma. Analysis of 3,990 sequences deposited between 1985 and 2017 allowed us to highlight a worldwide increasing prevalence of HIV-1 mutants expressing vp17s over time. Since genomic surveillance uncovered a cluster of HIV-1 expressing a B cell clonogenic vp17 dated from 2011 to 2019, we conclude that aa insertions can be fixed in HIV-1 and that mutant viruses displaying B cell clonogenic vp17s are actively spreading.
