HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide

Caccuri, F; Messali, S; Zani, A; Campisi, G; Giovanetti, M; Zanussi, S; Vaccher, E; Fabris, S; Bugatti, A; Foca, E; Castelli, F; Ciccozzi, M; Dolcetti, R; Gallo, RC; Caruso, A

Author(s): Caccuri, F; Messali, S; Zani, A; Campisi, G; Giovanetti, M; Zanussi, S; Vaccher, E; Fabris, S; Bugatti, A; Foca, E; Castelli, F; Ciccozzi, M; Dolcetti, R; Gallo, RC; Caruso, A;
Details: Publication Year 2022-07-05,Volume 119,Issue #27,Page e2122050119
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Publication Type: Research article
Abstract: 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.
Keywords: *B-Lymphocytes/virology; Genetic Variation; *HIV Antigens/genetics; *HIV-1/genetics/isolation & purification; Humans; *Lymphoma, AIDS-Related/epidemiology/virology; Prevalence; Retrospective Studies; *gag Gene Products, Human Immunodeficiency Virus/genetics; B cell p17 variants; Hiv-1; antiretroviral therapy; lymphoma; proteins
Department(s): Laboratory Research
PubMed ID: 35763571
Publisher's Version: https://doi.org/10.1073/pnas.2122050119
Open Access at Publisher's Site: https://doi.org/10.1073/pnas.2122050119
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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