Abstract
Restriction factors are structurally and functionally diverse cellular proteins that constitute a first line of defense against viral pathogens. Exceptions exist, but typically these proteins are upregulated by interferons (IFNs), target viral components, and are rapidly evolving due to the continuous virus–host arms race. Restriction factors may target HIV replication at essentially each step of the retroviral replication cycle, and the suppression of viral transcription and the degradation of viral RNA transcripts are emerging as major innate immune defense mechanisms. Recent data show that some antiviral factors, such as the tripartite motif-containing protein 22 (TRIM22) and the γ-IFN-inducible protein 16 (IFI16), do not target HIV-1 itself but limit the availability of the cellular transcription factor specificity protein 1 (Sp1), which is critical for effective viral gene expression. In addition, several RNA-interacting cellular factors including RNAse L, the NEDD4-binding protein 1 (N4BP1), and the zinc finger antiviral protein (ZAP) have been identified as important immune effectors against HIV-1 that may be involved in the maintenance of the latent viral reservoirs, representing the major obstacle against viral elimination and cure. Here, we review recent findings on specific cellular antiviral factors targeting HIV-1 transcription or viral RNA transcripts and discuss their potential role in viral latency.
Highlights
Since the beginning of the pandemic, about 80 million people have been infected with HIV-1 and approximately half of them have died of AIDS
These numbers are still sobering, they illustrate that significant progress has been made in the fight against AIDS, because the availability of combined antiretroviral therapy has allowed for the reduction of AIDS-related deaths by more than half since the peak in 2004
It has been reported that zinc finger antiviral protein (ZAP) might play a role in regulating herpesvirus latency [103], and the knock-down of endogenous ZAP moderately enhanced the expression of Human T-cell leukaemia virus type 1 (HTLV-1) mRNA and proteins [104]
Summary
Since the beginning of the pandemic, about 80 million people have been infected with HIV-1 and approximately half of them have died of AIDS. One approach to target these reservoirs that is intensively pursued is the so called “shock/ kick and kill” approach [5,6] It involves two major steps, i.e., treatment with a combination of latency-reversing agents to reactivate latent HIV hiding in the immune cells (the “shock/kick”), and targeting them for elimination by immune mechanisms (the “kill”) while preventing new infections by cART. The establishment and maintenance of HIV-1 latency is determined by numerous mechanisms These involve the availability of cellular transcription and elongation factors, epigenetic modifications, the site of proviral integration, as well as effectiveness of RNA splicing, nuclear export, translation and immune clearance of virally infected cells [3,4,10,11,12,13,14]. We hope that the present review will encourage further studies on the potential role of cellular factors modulating viral transcription and targeting viral RNA transcripts in HIV latency
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
