Background: Viroporins are virally encoded ion channels that are involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporin proteins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 370 amino acid protein known as Orf3a. Here, we compared the HIV-1 virus infectivity in the presence of four different β-coronavirus E proteins.
Results: We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, we show that the E proteins reduced the levels of HIV-1 protein synthesis in cells and that that the E protein neither affected reverse transcription nor genome integration. However, SARS-CoV-2 E protein activated the ER-stress pathway associated with the phosphorylation of eIF-2α, which is known to attenuate protein synthesis in cells. Other ever-expressed proteins (HSV-1 gD, HIV-1 gp160 and EGFP) did not cause phosphorylation of eIF-2α. Finally, we show that unlike the Vpu protein of HIV-1 and the Spike protein of SARS-CoV-2, the four E proteins and the SARS-CoV-2 N protein did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2).
Conclusions: The results of this study indicate that while viroporins from homologous viruses can enhance virus release, that we show a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and virus release.