Novel host restriction factors implicated in HIV-1 replication

Abstract

Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

“…In cattle, apolipoprotein B-100, apolipoprotein A-I and apolipoprotein C-III have previously been identified as biomarkers for fatty liver and related diseases [181]. In other taxa, apolipoproteins have also been found to display antimicrobial activity against a range of pathogenic bacteria [182][183][184][185] as well as against viral (HIV) replication [186]. Various apolipoproteins have recently been identified as deimination protein candidates by our group in several taxa [15,16,92,93,99].…”

Why was PERV not transmitted during preclinical and clinical xenotransplantation trials and after inoculation of animals?

“…Recently novel cellular restriction factors implicated in HIV-1 replication have been described [ 70 ] and it has to be analysed whether these proteins or other factors still unknown may also inhibit PERV.…”

Enterovirus 71 antagonizes the inhibition of the host intrinsic antiviral factor A3G

“…In addition to cytidine deaminase activity, another characteristic of A3G, its nucleic acid binding activity, also contributes to its virus inhibitory function ( 21 , 25 , 26 ). However, viruses have developed sophisticated strategies to evade host antiviral factors to replicate efficiently in host cells ( 27–29 ). HIV-1 is well known to thwart this restriction through its accessory protein viral infectivity factor (Vif), which degrades the A3G protein and inactivates A3G anti-viral activity by recruiting the Cullin5-ElonginB-ElonginC-CBFβ E3 ubiquitin ligase through a proteasome pathway ( 30–32 ).…”