AUTHOR=Sood Vikas , Lata Sneh , Ramachandran Vishnampettai G. , Banerjea Akhil C. TITLE=Suppressor of Cytokine Signaling 3 (SOCS3) Degrades p65 and Regulate HIV-1 Replication JOURNAL=Frontiers in Microbiology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00114 DOI=10.3389/fmicb.2019.00114 ISSN=1664-302X ABSTRACT=

Human Immunodeficiency Virus-1 (HIV-1) is known to induce the expression of SOCS3 which is a negative feed-back regulator of inflammatory responses. Here, we demonstrate that reactivation of latent HIV-1 leads to degradation of SOCS3 at early time points. Interestingly, SOCS3 degradation following transfection of HIV-1 RNA as well as polyIC in THP-1 cells further confirmed the role of viral RNA signaling in SOCS3 biology. Degradation of SOCS3 contributes toward viral RNA induced inflammatory responses. NF-κB signaling is also induced upon HIV-1 infection which leads to the production of pro-inflammatory cytokines to control the viral spread. Further investigations revealed that SOCS3 inhibits the expression and activity of p65 by interacting with it and inducing its ubiquitin-dependent proteasomal degradation. SH2 domain was critical for SOCS3-p65 interaction and p65 degradation. We also found that expression of SOCS3 promotes HIV-1 replication. Thus, HIV-1 downregulates SOCS3 in early phase of infection to promote inflammatory responses for large production of activated cells which are suitable for viral spread and induces SOCS3 later on to limit inflammatory responses and ensure viral survival.