APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz

Abstract

Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4+ cell count and CD4+/CD8+ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies.

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression

“…MDMs upon CCL2 neutralization, as well as in PBMCs of HIV-1-infected subjects treated with the CCR5/CCR2 inhibitor cenicriviroc. This effect was associated with reduced levels of viral DNA accumulation in macrophages and of the inflammatory marker soluble CD14 in infected individuals (20,54). It is worth noting that APOBEC3A restricts HIV-1 replication acting at postentry steps of the virus life cycle, which are indeed those demonstrated to be affected by CCL2 blocking.…”

Mechanistic Insight into Antiretroviral Potency of 2′-Deoxy-2′-β-fluoro-4′-azidocytidine (FNC) with a Long-Lasting Effect on HIV-1 Prevention

“…In addition, FNC has an advantage in that it can restore A3G expression more successfully than other clinically used antiretroviral regimens. The long-term (48 weeks) treatment of patients with cenicriviroc (CVC) or efavirenz (EFV) did not upregulate A3G expression, but a slight increase of APOBEC3A, another member of the APOEC3 family, was observed in the CVC treatment …”

Avaliação da Exposição ao Risco Ocupacional Calor em Policiais na Cidade de Caraguatatuba

“…Dessa forma, presente na superfície dos macrófagos, as proteínas receptoras CCR5, às quais o retrovírus HIV se acoplaria e fundiria a membrana celular e viral, são inibidas, impedindo, então, a invasão a célula hospedeira. Estudos mostram que, apesar dos diferentes efeitos virais extracelulares em relação ao maraviroc, o cenicriviroc, antagonista dos co-receptores de quimiocinas 5 e 2 (CCR5 e CCR2), é capaz de promover, após 4h, um menor grau de DNA viral dentro da célula-alvo, sendo, ainda, sugerido como um potencial anti-inflamatório durante a progressão da AIDS (COVINO et al, 2018;DE LUCA et al, 2019;KRAMER et al, 2015).…”