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; Marina Jerebtsova; Sergei Nekhai

doi:10.1016/j.isci.2024.108813

Antiviral response and HIV-1 inhibition in sickle cell disease

iScience. 2024 Jan 6;27(2):108813. doi: 10.1016/j.isci.2024.108813. eCollection 2024 Feb 16.

Authors

Namita Kumari^{1

2}, Asrar Ahmad¹, Clemilson Berto-Junior^{1

3}, Andrey Ivanov¹, Fayuan Wen¹, Xionghao Lin¹, Sharmin Diaz¹, Iheanyi Okpala⁴, James G Taylor^{1

2

5}, Marina Jerebtsova⁶, Sergei Nekhai^{1

2

6}

Affiliations

¹ Center for Sickle Cell Disease, Howard University, Washington, DC, USA.
² Department of Medicine, Howard University, Washington, DC, USA.
³ Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁴ University of Nigeria, Enugu, Nigeria.
⁵ Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada.
⁶ Department of Microbiology, Howard University, Washington, DC, USA.

Abstract

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.

Keywords: Hematology; Virology.

Abstract

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