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
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.
