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Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case–control study

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Abstract

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.

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Funding

KM was funded by the Discovery Foundation Academic Fellowship Award and the South African Medical Association Research Master’s Scholarship. MIC was funded by the South African National Research Foundation “Incentive Funding for Rated Researchers” scheme: Grant number 85526.

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Authors and Affiliations

  1. Division of Neurology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

    Kate McMullen, Kathleen Bateman, Alan Stanley & Alan Bryer

  2. Division of Geriatric Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

    Marc Combrinck

  3. Division of Medical Virology, Stellenbosch University and National Health Laboratory Services, Cape Town, South Africa

    Susan Engelbrecht

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  1. Kate McMullen
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  2. Kathleen Bateman
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  3. Alan Stanley
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  4. Marc Combrinck
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  5. Susan Engelbrecht
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  6. Alan Bryer
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Correspondence to Kate McMullen.

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McMullen, K., Bateman, K., Stanley, A. et al. Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case–control study. J. Neurovirol. 27, 137–144 (2021). https://doi.org/10.1007/s13365-020-00936-y

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  • DOI: https://doi.org/10.1007/s13365-020-00936-y

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