Figure 2.

Comparative overview of viral entry and receptor downregulation. Schematic representation of a host cell potentially co-infected with HIV (left side) and SARS-CoV-2 (right side). [1] Binding of HIV or SARS-CoV-2 to key receptors. Both SARS-CoV-2 require initial interaction with specific receptors at the cell membrane: HIV binds to CD4 and co-receptors CCR5 and CXCR4 (left) and SARS-CoV-2 binds to host cell receptors CD147 or ACE2 (right). Binding of SARS-CoV-2 to ACE2 receptor requires initial cleavage of the viral S1 glycoprotein assisted by human protease TMPRSS2 so that viral S2 protein can be internalized along with the rest of the virion (right). [2] Entry of virus into cell. HIV fusion with the cell membrane leads to disassembly of the virion in the cytoplasm, leading to the release of viral genetic material, reverse transcription and [4] eventual integration of viral DNA into the host cell DNA, whereas SARS-CoV-2 enters the cell through endocytosis after binding to ACE2 or CD147. [3] Downregulation of CD4 by NEF or ACE2 by ADAM17. Viral internalization (infection) leads to downregulation of the initial entry receptor for HIV (CD4, mediated by the viral Nef polypeptide) and ACE2 for SARS-CoV-2, which is cleaved by the host ADAM17. [5] Fusion of the endosome and the virus. The viral membrane and endosome membrane fuse, releasing SARS-CoV-2’s genome into the host cell. Illustration credit: Nicholas J. Evans.