Skip to main content

REVIEW article

Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1458195

Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections?

Provisionally accepted

The final, formatted version of the article will be published soon.

    This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in the pathogenesis of SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on the vascular endothelium. The processes involved in vascular homeostasis and angiogenesis are reviewed briefly before exploring the interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), and inflammatory pathways. We then focus on SARS-CoV-2 infection and show how binding of the viral pathogen to the angiotensin-converting enzyme 2 receptor, as well as to NRP-1, leads to elevated levels of VEGF-A and consequences such as coagulation, vascular dysfunction, and inflammation. HIV infection augments angiogenesis via several mechanisms, most prominently, by trans-activator of transcription (tat) protein mimicking VEGF-A by binding to its receptor, VEGFR-2, as well as upregulation of NRP-1, which enhances the interaction between VEGF-A and VEGFR-2. We propose that the elevated levels of VEGF-A observed during HIV/SARS-CoV-2 co-infection originate predominantly from activated immune cells due to upregulation of HIF-1α by damaged endothelial cells. In this context, a few clinical trials have described diminished requirement for oxygen therapy during anti-VEGF treatment of SARS-CoV-2 infection. The currently available anti-VEGF therapy strategies target the binding of VEGF-A to both VEGFR-1 and VEGFR-2. Blocking of both receptors could, however, lead to a negative outcome, inhibiting not only pathological, but also physiological angiogenesis. Based on examination of published studies, it is proposed that selective targeting of VEGFR-1 may be beneficial in the context of treatment of SARS-CoV-2 infection.

    Keywords: Chemokines, COVID-19, Cytokines, HIV, SARS-CoV-2, VEGF

    Received: 02 Jul 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Van Der Mescht, Steel, Anderson and Rossouw. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Mieke A. Van Der Mescht, University of Pretoria, Pretoria, South Africa
    Theresa M. Rossouw, University of Pretoria, Pretoria, South Africa

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.