The strengthening/bundling of cortical actin filaments results in co-receptor clustering, increasing the probability of interaction towards the HIV-CD4 complex. This process is referred to as actin polymerization ( Figure 1A). This leads to downstream phosphorylation of ROCK/LIMK-1 to inactivate actin-depolymerization factor (ADF) cofilin-1. HIV-CD4/CXCR4/CCR5 activates Rho family GTPases to exchange GDP for GTP. HIV-1 interaction with CD4 remains an obstacle to viral entry. HIV-1 targets CD4+ cells with CXCR4/CCR5 co-receptors such as monocytes/macrophages, dendritic, and T-helper cells. Additionally, PKR and IRE1α show to be key regulators in cofilin-1 phosphorylation and viral restriction. Our findings show that PSP treatment before infection leads to an overall lower infectivity.

PKR/IRE1α inhibitors were used to validate viral entry and cofilin-1 phosphorylation through Western blots. Validation of key proteome markers was done through RT-qPCR. PKR, IRE1α, and cofilin-1 biomarkers were measured through immunoblots. Quantitative proteomics was performed to analyze cytoskeletal and UPR regulators. HIV-1 p24 antigen was measured through infected supernatant to determine PSP’s restrictive potential. In the present study, we examined the roles of PKR and IRE1α in cofilin-1 phosphorylation and its HIV-1 restrictive roles in THP1. However, its involvement towards viral infectivity has not been elucidated before.

In our published findings, Coriolus versicolor bioactive extract polysaccharide peptide (PSP) has demonstrated anti-HIV replicative properties in THP1 monocytic cells. The unfolded protein response (UPR) marker Inositol-Requiring Enzyme-1α (IRE1α) and interferon-induced protein (IFN-IP) double-stranded RNA- activated protein kinase (PKR) are reported to overlap with actin components. Disruption of ADF signaling is associated with denial of entry. HIV-1 manipulates cofilin-1 regulation as a pre- and post-entry requisite.

Actin depolymerization factor (ADF) cofilin-1 is a key cytoskeleton component that serves to lessen cortical actin.

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