Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

Abstract

The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs) containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1), Staufen double-stranded RNA binding protein 1/2 (STAU1/2), or components of miRNA-induced silencing complex (miRISC) and processing bodies (PBs). More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A), allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries.

The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level

“…In order to promote their survival, viruses have evolved numerous strategies to either evade or manipulate the RNA surveillance pathways (reviewed in [ 32 ]). Retroviruses, despite containing long 3′UTRs that are recognised by UPF1, are capable of evading NMD by virtue of the presence of RNA stability elements in their genome [ 33 ] (reviewed in [ 34 , 35 ]). In previous studies, our group has demonstrated that HIV-1 not only evades NMD, it also hijacks UPF1 to form an RNP that promotes vRNA stability and nucleocytoplasmic export [ 36 , 37 ].…”

Virus infection-induced host mRNA degradation and potential application of live cell imaging

“…Recently, the HIV-1 unspliced mRNA has been shown to contain N6-methyladenosine (m 6 A), allowing the recruitment of YTH N 6 methyladenosine RNA binding protein 2 (YTHDF2), which is involved in mRNA decay. This indicates that HIV-1 interacts with host mRNA decay components to accomplish viral replication successfully [39]. This finding implicates a novel mechanism involved in infection-induced host RNA degradation.…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…YTHDF2 is a negative regulator of interferon response as it facilitates the fast turnover of interferon mRNAs and consequently helps viral propagation [110]. YTHDF2 plays positive roles in viral gene expression and HIV-1 particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication [111,112]. Overexpression of YTHDF2 induces more rapid viral replication, and larger viral plaques, in SV40 infected BSC40 cells [113].…”