gp120 Envelope Glycoproteins of HIV-1 Group M Subtype A and Subtype B Differentially Affect Gene Expression in Human Vascular Endothelial Cells

Cardiovascular complications are seen among human immunodeficiency virus (HIV)-positive individuals, who now survive longer due to successful antiretroviral therapies. Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased blood pressure in the lung circulation. The prevalence of PAH in the HIV-positive population is dramatically higher than that in the general population. While HIV-1 Group M Subtype B is the most prevalent subtype in western countries, the majority of HIV-1 infections in eastern Africa and former Soviet Union countries are caused by Subtype A. Research on vascular complications in the HIV-positive population in the context of subtype differences, however, has not been rigorous. Much of the research on HIV has focused on Subtype B, and information on the mechanisms of Subtype A is nonexistent. The lack of such knowledge results in health disparities in the development of therapeutic strategies to prevent/treat HIV complications. The present study examined the effects of HIV-1 gp120 of Subtypes A and B on human pulmonary artery endothelial cells by performing protein arrays. We found that the gene expression changes caused by gp120s of Subtypes A and B are different. Subtype A is a more potent downregulator of perostasin, matrix metalloproteinase-2, and ErbB than Subtype B, while Subtype B is more effective in downregulating monocyte chemotactic protein-2 (MCP-2), MCP-3, and thymus- and activation-regulated chemokine proteins. This is the first report of gp120 proteins affecting host cells in an HIV subtype-specific manner, opening up the possibility that complications occur differently in HIV patients throughout the world.

https://pubmed.ncbi.nlm.nih.gov/36834948/

Mucosal AIDS virus transmission is enhanced by antiviral IgG isolated early in infection

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631165/

HIV-1 gp120 Protein Activates Cyclin-Dependent Kinase 1, a Possible Link to Central Nervous System Cell Death

Human immunodeficiency virus-1 (HIV-1)-associated neurodegenerative disorder (HAND) is frequently reported in HIV-infected individuals. The gp120 envelope viral protein has been implicated in the pathogenesis of HAND in HIV-1-infected patients; however, its pathogenic mechanism remains unclear. In this study, we first overexpressed gp120 proteins in pc12 cells and used PI staining, a CCK8 assay, a TUNEL assay, and caspase-9/caspase-3-induced apoptosis to ascertain the mediated cell death. Subsequently, the gp120-overexpressed cells were subjected to RNA transcriptomics and mass spectrometry. The obtained results were integrated and validated using a quantitative polymerase chain reaction (qPCR) and the postmortem brain samples with HIV-associated dementia were analyzed against the normal control (using the GSE35864 data set on gene ontology omnibus repository). Upon the integration of the RNA transcriptomic and proteomic results, 78 upregulated genes were revealed. Fut8, Unc13c, Cdk1, Loc100359539, and Hspa2 were the top five upregulated genes. Upon the analysis of the GSE35864 data set, the results indicate that Cdk1 was upregulated in HIV-associated dementia in comparison to the normal control. Moreover, the protein expression of Cdk1 was significantly higher in the gp120 transfected group compared to the normal control and decreased significantly upon inhibition using Roscovitine (a known Cdk1 inhibitor). Taken together, our results provide a possible molecular signature of the neurological impairment secondary to HIV glycoprotein 120.

Antigenic hypervariation has been more effectively adopted by RNA viruses than DNA viruses, most likely because of the higher mutational frequency of RNA replicases compared to most viral DNA polymerases (Elena and Sanjuan, 2005). In some cases, such as Hepatitis C and HIV, the antigenic drift rate is so rapid that it effectively outpaces not only development of an effective immune response in the individual infected host but also confounds our attempts to develop prophylactic vaccines (Bowen and Walker, 2005, Derdeyn and Silvestri, 2005, Letvin, 2005, Wieland and Chisari, 2005). In general, viral RNA replicases lack proofreading capacity and generate swarms of genetic variants of progeny viruses that become subject to selection pressure for fitness, particularly in the form of immune bypass variants. However, even DNA viruses can undergo significant levels of mutational drift and thus become subject to immune selection. For example, single-stranded DNA viruses can exhibit mutational frequencies that rival the RNA viruses (Shackelton et al., 2005), and even double-stranded DNA viruses with high-fidelity polymerases like cytomegalovirus can still spin off a sufficiently diverse set of progeny to permit selective escape from host elements of innate immunity, such as NK cell clearance (French et al., 2004).