Restriction of HIV-1 infection in sickle cell trait

• Type of Material: Article
• Authors: Namita Kumari, Howard University; Mehdi Nouraie, University of Pittsburgh; Asrar Ahmad, Howard University; Hatajai Lassiter, Howard University; Javed Khan, Howard University; Sharmin Diaz, Howard University; Nowah Afangbedji, Howard University; Songping Wang, Howard University; Patricia E Houston, Howard University; Tatiana Ammosova, Howard University; Miguel de Mulder Rougvie, Weill Cornell Medicine; Sohail Rana, Howard University; Douglas F Nixon, Weill Cornell Medicine; Kathryn Anastos, Montefiore Medical Center; Jason Lazar, SUNY Downstate Medical Center; Audrey L French, John H. Stroger Jr. Hospital of Cook County; Stephen Gange, Johns Hopkins University; Adaora A Adimora, University of North Carolina; M. Neale Weitzmann, Emory University; Margaret Fischl, University of Miami; Mirjam-Colette Kempf, University of Alabama Birmingham; Seble Kassaye, Georgetown University; James G Taylor, Howard University; Sergei Nekhai, Howard University
• Language: English
• Date: 2021-11-30
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by The American Society of Hematology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021004247
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 5
• Issue: 23
• Start Page: 4922
• End Page: 4934
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (P50-HL118006 and R01-HL125005), the National Institute on Minority Health and Health Disparities (G12-MD007597), and the National Institute of Allergy and Infectious Diseases (UM1-AI26617, P50-AI150476 and P30-AI087714 [District of Columbia Center for AIDS Reseach]).
• Keywords: PREVALENCE; Life Sciences & Biomedicine; Hematology; GENE; MALARIA; DISEASE PROGRESSION; Science & Technology; EXPRESSION; IRON; ACTIVATION; HIV-1-INFECTED PATIENTS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Public Health

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.