期刊
BLOOD ADVANCES
卷 5, 期 23, 页码 4922-4934出版社
ELSEVIER
DOI: 10.1182/bloodadvances.2021004247
关键词
-
类别
资金
- National Institutes of Health, National Heart, Lung, and Blood Institute [P50-HL118006, R01-HL125005]
- National Institute on Minority Health and Health Disparities [G12-MD007597]
- National Institute of Allergy and Infectious Diseases [UM1-AI26617, P50-AI150476, P30-AI087714]
- Atlanta clinical research center (CRS) [U01-HL146241]
- Baltimore CRS [U01-HL146201]
- Bronx CRS [U01-HL146204]
- Brooklyn CRS [U01-HL146202]
- Data Analysis and Coordination Center [U01-HL146193]
- Chi-cago-Cook County CRS [U01-HL146245]
- Connie Wofsy Women's HIV Study, Northern California CRS [U01-HL146242]
- Metropolitan Washington CRS [U01-HL146205]
- Miami CRS [U01-HL146203]
- UAB-MS CRS [U01-HL146192]
- UNC CRS [U01-HL146194]
- National Heart, Lung, and Blood Institute
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute on Aging
- National Institute of Dental and Craniofacial Research
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Nursing Research
- National Cancer Institute
- National Institute on Alcohol Abuse and Alco-holism
- National Institute on Deafness and Other Communica-tion Disorders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute on Minority Health and Health Disparities
- National Institutes of Health, Office of AIDS Research
- University of California at San Francisco Clinical and Translational Science Institute [UL1-TR000004]
- Atlanta Center for AIDS Research [P30-AI050409]
- University of North Carolina Center for AIDS Research [P30-AI050410]
- University of Alabama at Biminghem Center for AIDS Research [P30-AI027767]
Individuals with sickle cell trait (SCT) exhibit a restriction of HIV-1 infection characterized by higher levels of HO-1 and lower levels of HIV-1 replication. This suggests that factors like HO-1 and RNR2 may limit HIV-1 pathogenicity among those with SCT.
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 HN-1 replication and lower levels of HIV-1 reverse transcription products, 2-long terminal repeat cirde, 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 WINS (Women Interagency HIV-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据