Antiviral response and HIV-1 inhibition in sickle cell disease

Namita Kumari; Asrar Ahmad; Clemilson Berto-Junior; Andrey Ivanov; Fayuan Wen; Xionghao Lin; Sharmin Diaz; Iheanyi Okpala; James G. Taylor, VI; Marina Jerebtsova; Sergei Nekhai

iScience (Feb 2024)

Antiviral response and HIV-1 inhibition in sickle cell disease

Namita Kumari,
Asrar Ahmad,
Clemilson Berto-Junior,
Andrey Ivanov,
Fayuan Wen,
Xionghao Lin,
Sharmin Diaz,
Iheanyi Okpala,
James G. Taylor, VI,
Marina Jerebtsova,
Sergei Nekhai

Affiliations

Namita Kumari: Center for Sickle Cell Disease, Howard University, Washington, DC, USA; Department of Medicine, Howard University, Washington, DC, USA
Asrar Ahmad: Center for Sickle Cell Disease, Howard University, Washington, DC, USA
Clemilson Berto-Junior: Center for Sickle Cell Disease, Howard University, Washington, DC, USA; Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Andrey Ivanov: Center for Sickle Cell Disease, Howard University, Washington, DC, USA
Fayuan Wen: Center for Sickle Cell Disease, Howard University, Washington, DC, USA
Xionghao Lin: Center for Sickle Cell Disease, Howard University, Washington, DC, USA
Sharmin Diaz: Center for Sickle Cell Disease, Howard University, Washington, DC, USA
Iheanyi Okpala: University of Nigeria, Enugu, Nigeria
James G. Taylor, VI: Center for Sickle Cell Disease, Howard University, Washington, DC, USA; Department of Medicine, Howard University, Washington, DC, USA; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada
Marina Jerebtsova: Department of Microbiology, Howard University, Washington, DC, USA
Sergei Nekhai: Center for Sickle Cell Disease, Howard University, Washington, DC, USA; Department of Medicine, Howard University, Washington, DC, USA; Department of Microbiology, Howard University, Washington, DC, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 2
p. 108813

Abstract

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Summary: Sickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion, and ischemia. HIV-1 infection was previously shown to be suppressed in SCD PBMCs. Here, we report that HIV-1 suppression is attributed to the increased expression of iron, hypoxia, and interferon-induced innate antiviral factors. Inhibition of upregulated antiviral genes, HMOX-1, CDKN1A, and CH25H, increased HIV-1 replication in SCD PBMCs, suggesting their critical role in HIV-1 suppression. Levels of IFN-β were elevated in SCD patients. Sickle cell hemoglobin (HbS) treatment of THP-1-derived and primary monocyte-derived macrophages induced production of IFN-β, upregulated antiviral gene expression, and suppressed HIV-1 infection. Infection with mouse-adapted EcoHIV was suppressed in the SCD mice that also exhibited elevated levels of antiviral restriction factors. Our findings suggest that hemolysis and release of HbS leads to the induction of IFN-β production, induction of cellular antiviral state by the expression of iron and IFN-driven factors, and suppression of HIV-1 infection.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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