Anti-HIV type 1 Glycoprotein 120, Glycoprotein 160 polyclonal antibody

The innate immune restriction factor SAMHD1 can inhibit diverse viruses in myeloid cells. Mechanistically, SAMHD1 inhibits lentiviral replication including HIV-1 by depleting the nucleotide pool to interfere with their reverse transcription. Equine infectious anemia virus (EIAV) is an ancient lentivirus that preferentially attacks macrophages. However, the mechanism by which EIAV successfully establishes infection in macrophages with functional SAMHD1 remains unclear. Here, we demonstrate that while equine SAMDH1 can limit EIAV replication in equine macrophages at the reverse transcription stage, the antiviral effect is counteracted by the well-known transcriptional regulator Rev, which downregulates equine SAMHD1 through the lysosomal pathway. Remarkably, Rev hijacks BECN1 (beclin 1) and PIK3C3 to mediate SAMHD1 degradation in a canonical macroautophagy/autophagy-independent pathway. Our study illustrates that equine lentiviral Rev possesses important functions in evading cellular innate immunity in addition to its RNA regulatory function, and may provide new insights into the co-evolutionary arms race between SAMHD1 and lentiviruses.

Objectives: This study aims to analyze the association of the presence of common polymorphisms [single nucleotide polymorphisms (SNPs)] on Toll-like receptors (TLRs), such as TLR9-1635A/G, TLR2-1892A/C, TLR2-2258G/A, TLR4-899A/G, and TLR4-1196C/T, with the viral rebound after stopping antiretroviral treatment (ART). CCR5-Delta 32 deletion and HLA-A/HLA-B alleles were also analyzed. Design: Interruption of ART may be required to investigate the outcome of strategies aimed to achieve drug-free HIV remission or cure. However, interruption of ART is currently not indicated. This was a retrospective longitudinal study that included 57 long-term suppressed HIV-1-infected individuals. Methods: TLR SNPs were detected by real-time polymerase chain reaction (PCR). CCR5-Delta 32 was analyzed by conventional PCR and HLA-A and HLA-B alleles by PCR-SSOP Luminex. Results: HIV-1 RNA rebound at week 4 after treatment interruption positively correlated with pre-ART HIV-1 load (P= 0.025). The TLR9-1635AA genotype was independently associated with a higher HIV-1 rebound compared with those with AG + GG genotype (multivariate stepwise regression analysis,P= 0.004). Women had lower HIV-1 RNA load both at rebound and during the 72 weeks of follow-up compared with men (P< 0.05 at all time-points), whereas CD4 nadir and CD4 count set-point were similar according to sex. The pre-ART viral load was independently associated with the viral set-point (P= 0.001), whereas the presence of the HLA-A01 allele (P= 0.027) and the CD4 nadir (P= 0.001) were associated with the CD4 count set-point. Conclusions: The association of the TLR9-1635AA genotype with a higher HIV-1 rebound suggests that this SNP may affect the results from strategies requiring interruption of ART aimed to cure HIV-1 infection.