Restriction of HIV-1 infection in sickle cell trait

Namita Kumari, Mehdi Nouraie, Asrar Ahmad, Hatajai Lassiter, Javed Khan, Sharmin Diaz, Nowah Afangbedji, Songping Wang, Patricia E. Houston, Tatiana Ammosova, Miguel De Mulder Rougvie, Sohail Rana, Douglas F. Nixon, Kathryn Anastos, Jason Lazar, Audrey L. French, Stephen Gange, Adaora A. Adimora, M. Neale Weitzmann, Margaret FischlMirjam Colette Kempf, Seble Kassaye, James G. Taylor, Sergei Nekhai

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection. Ex vivo infection of SCT PBMCs exhibited an approximately twofold reduction of HIV-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat circle, HIV-1 integration, and gag RNA expression. SCT PBMCs had higher HO-1 messenger RNA (mRNA) and protein levels and reduced ribonucleotide reductase 2 (RNR2) protein levels. HO-1 inhibition by tin porphyrin eliminated ex vivo HIV-1 restriction. Among Howard University clinic recruits, higher levels of HO-1 and RNR2 mRNA and lower HIV-1 env mRNA levels were found in SCT individuals living with HIV-1. To determine the population-level effect of SCT on HIV-1 prevalence, we assessed SCT among women living with HIV (WLH) in the WIHS (Women InteragencyHIV-1 Study). Among WIHS African-American participants, the prevalence of SCT was lower among women with HIV compared with uninfected women (8.7% vs 14.2%; odds ratio, 0.57; 95% confidence interval, 0.36-0.92; P = .020). WIHS WLH with SCT had higher levels of CD4+/CD8+ ratios over 20 years of follow-up (P = .003) than matched WLH without SCT. Together, our findings suggest that HIV-1 restriction factors, including HO-1 and RNR2, might restrict HIV-1 infection among individuals with SCT and limit the pathogenicity of HIV.

Original languageEnglish (US)
Pages (from-to)4922-4934
Number of pages13
JournalBlood Advances
Volume5
Issue number23
DOIs
StatePublished - Dec 14 2021
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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