Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles

Venkatachari, Narasimhan J.; Walker, Leah A.; Taştan, Öznur; Le, Thien P; Dempsey, Timothy; Li, Yaming; Yanamala, Naveena; Srinivasan, Alagarsamy; Klein‐Seetharaman, Judith; Montelaro, Ronald C.; Ayyavoo, Velpandi

doi:10.1186/1743-422x-7-119

Cited by 27 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this purpose, we generated constructs containing TMPRSS2-ERG3 and TMPRSS2-ERG8 coding sequences fused to either N- or C-terminal coding sequences of the Venus reporter (Figure 4b). HIV-1 Vpr constructs were used as positive controls, as Vpr has been well characterized and shown to oligomerize [30]. As expected, we observed that VN-Vpr and VC-Vpr constructs co-transfected in HEK293 cells produced fluorescent signal, which was found to be localized in the nuclear region.…”

Section: Resultssupporting

confidence: 74%

Functional antagonism of TMPRSS2-ERG splice variants in prostate cancer

Rastogi

Tan

et al. 2014

Genes Cancer

Self Cite

View full text Add to dashboard Cite

The fusion between ERG coding sequences and the TMPRSS2 promoter is the most prevalent in prostate cancer (CaP). The presence of two main types of TMPRSS2-ERG fusion transcripts in CaP specimens, Type I and Type II, prompted us to hypothesize that the cumulative actions of different ERG variants may impact CaP development/progression. Using TMPRSS2-ERG3 (Type I) and TMPRSS2-ERG8 (Type II) expression vectors, we determined that the TMPRSS2- ERG8 encoded protein is deficient in transcriptional regulation compared to TMPRSS2-ERG3. Co-transfection of vectors resulted in decreased transcriptional regulation compared to TMPRSS2-ERG3 alone, suggesting transdominance of ERG8. Expression of exogenous ERG8 protein resulted in a decrease in endogenous ERG3 protein levels in TMPRSS2-ERG positive VCaP cells, with a concomitant decrease in C-MYC. Further, we showed a physical association between ERG3 and ERG8 in live cells by the bimolecular fluorescence complementation assay, providing a basis for the observed effects. Inhibitory effects of TMPRSS2-ERG8 on TMPRSS2- ERG3 were also corroborated by gene expression data from human prostate cancers, which showed a positive correlation between C-MYC expression and TMPRSS2-ERG3/TMPRSS2- ERG8 ratio. We propose that an elevated TMPRSS2-ERG3/TMPRSS2-ERG8 ratio results in elevated C-MYC in CaP, providing a strong rationale for the biomarker and therapeutic utility of ERG splice variants, along with C-MYC.

show abstract

Section: Resultssupporting

confidence: 74%

Functional antagonism of TMPRSS2-ERG splice variants in prostate cancer

Rastogi

Tan

et al. 2014

Genes Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Along those lines, previously published studies suggest that amino acid changes at niVpr positions 37 and 41 may affect Vpr oligomerization, which has been implicated in Vpr incorporation into nascent virions (Fritz et al , 2010; Venkatachari et al , 2010). Amino acids in this region of the protein (residues 36-46) have been shown to be critical for Vpr oligomerization (Zhao et al , 1994) and Vpr incorporation during virus assembly (Singh et al , 2000).…”

Section: Discussionmentioning

confidence: 86%

Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status

et al. 2016

View full text Add to dashboard Cite

Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50% of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences [neuropsychological impairment Vpr (niVpr) variants]. Amino acids N41 and A55 in the Vpr sequence were associated with more pronounced neurocognitive deficits (higher GDS). In contrast, amino acids I37 and S41 were connected to measurably lower GDS. All niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain.

show abstract

“…Based on the data, it was suggested that oligomerization of Vpr is essential for virion incorporation, and may also play a role in the events associated with virus infection (Venkatachari et al, 2010). In another study, BiFC was used to investigate intracellular interactions between APOBEC3G (A3G), RNA, and HIV-1 Gag.…”

Section: Virus-host Interactionsmentioning

confidence: 99%