Abstract
Human Immunodeficiency Virus type 1 (HIV-1) is the agent responsible for Acquired Immunodeficiency Syndrome (AIDS) and primarily targets CD4+ T lymphocytes, which are essential components of the immune system. The viral genome, initially thought to comprise nine genes transcribed from the sense strand of the proviral DNA, also includes a tenth gene called “asp,” transcribed from the antisense strand and encoding the ASP (AntiSense Protein). Despite the discovery of this gene in 1988, no function had been described for the ASP protein.In 2019, a study revealed the presence of the ASP protein on the surface of viral particles and on the plasma membranes of infected cells, notably colocalizing with the viral envelope protein, gp120. This study led us to hypothesize that the ASP protein might play a role in the viral entry process. Our research project, therefore, aimed to investigate the role of the ASP protein in the entry of the virus into the host cell.The results obtained show that: HIV-1 viruses lacking expression of the ASP protein display a lower replication rate in target cells compared to wild-type HIV-1 viruses expressing ASP. These same viruses exhibit reduced fusion-mediated entry compared to viruses that contain the ASP protein. The absence of the ASP protein decreases the attachment of viruses to target cells.Furthermore, we demonstrated that the expression of ASP in cells constitutively expressing the envelope proteins gp120/gp41 significantly increases the amount of syncytia formed, and that this effect requires the presence of the protein’s first transmembrane domain. Finally, our preliminary results on the impact of ASP expression at the plasma membrane indicate that this protein increases plasma membrane fluidity.Taken together, these findings suggest, for the first time, that one of the functions of the ASP protein (although we cannot rule out the possibility that ASP may have additional roles) is to promote the entry of HIV-1 into target cells. This function of ASP may have contributed to facilitating HIV-1 transmission and possibly played a role in the pandemic success of group M viruses.