The Envelope Protein Of SARS-Cov-2 Potently Inhibits HIV-1 Infection


A new study by researchers from University of Kansas Medical Center-USA has found that the envelope protein of SARS-Cov-2 potently inhibits HIV-1 infection.

The study findings were published on a preprint server and are currently being peer reviewed.

The recent introduction of the highly transmissible coronavirus SARS-CoV-2 into the human population has resulted in the COVID-19 respiratory disease and pandemic (1–4). This has highlighted the urgent need to better understand the function of viral proteins in replication and virus pathogenesis.

The human pathogenic β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) contain four structural proteins (S, M, E, and N) (5, 6).

The spike (S) protein, the largest protein within virions, binds to angiotensin converting enzyme 2 (ACE-2) receptor, and is the major target for neutralizing antibodies. The membrane (M) protein, the most abundant protein of the virion, is thought to form a scaffold in the ER-Golgi intermediate compartment (ERGIC), the site of virus maturation (7,8). The nucleocapsid (N) of SARS-CoV binds to the viral RNA and together with E and M can form viral particles (9).

The E protein of the β-coronaviruses is the smallest and least abundant virion protein. This transmembrane protein (75-84 amino acids in length) is predicted to have a short N-terminal domain, a hydrophobic transmembrane domain, and a longer cytoplasmic domain. Recent studies indicate that the E protein spans the membrane a single time with the N-terminal domain facing the lumen of the ER/ERGIC/Golgi (10–12).

While the expression of SARS-CoV E protein is dispensable for coronavirus replication, its deletion results in reduced virus growth, likely due to inefficient assembly (13–15). The E proteins of SARS-CoV-2 and SARS-CoV have 94% amino acid identity, differing at only four amino acid positions, while E proteins of MERS-CoV and HCoV-OC43 are more distantly related to SARS-CoV-2 E protein with approximately 37% and 25% amino acid identity, respectively. Interestingly, the E proteins of SARS-CoV-2 and several bat coronavirus isolates (RATG13, ZC45, and ZXC21) are identical.

The E proteins of coronaviruses have similarities to the Vpu protein of HIV-1 with respect to its size, orientation in the membrane, ion channel activity, and functions to enhance virus release (16–23). These similarities prompted us to examine the biological properties of the SARS-CoV-2 E protein in the context of HIV-1 replication.

Our results indicate that the SARS-CoV-2 E protein potently restricted HIV-1 infection. This restriction was not due to inhibition of viral integration or synthesis of viral RNA but rather correlates with the ability of the SARS-CoV-2 E protein to activate the phosphorylation of the eIF-2α, which is known to shutdown protein synthesis.

These results show for the first time that a viroporin (i.e., E protein) from SARS-CoV-2 that enhances virus infection can restrict a heterologous virus (i.e., HIV-1).


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