Pleiotropic Effects of HIV-1 Protein R (Vpr) on Morphogenesis and Cell Survival in Fission Yeast and Antagonism by Pentoxifylline
Overview
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Expression of HIV-1 Vpr causes cell cycle G2 arrest, change in cell shape, and cell death over a large evolutionary distance ranging from human to yeast cells. As a step toward understanding these highly conserved Vpr functions, we have examined the effect of Vpr on cytoskeletal elements and the viability of fission yeast. We demonstrate that the changes in cell morphology induced by Vpr in fission yeast are caused by several underlying cellular abnormalities, including increased biosynthesis of chitin in the cell wall, disruption of the actin cytoskeleton, and altered polarity for cell growth. The extent of these cellular alterations and cell survival correlates with the level of vpr expression. Accompanying cell death, Vpr induces aberrant nuclear morphologies in fission yeast which are similar to those found during the apoptosis induced by Vpr in mammalian cells. The Vpr-induced cytopathic effects and cell death can be suppressed by treatment with pentoxifylline, a compound that inhibits HIV-1 viral replication and suppresses Vpr-induced cell cycle G2 arrest in human and fission yeast cells. The results presented here suggest that pentoxifylline suppresses the effects of Vpr by blocking interactions of Vpr with cellular proteins. Given that pentoxifylline has potential therapeutic value in blocking the effects of Vpr in HIV-infected patients, understanding the molecular mechanisms by which pentoxifylline antagonizes Vpr may have general implications for HIV therapy.
Understanding the molecular mechanisms of human diseases: the benefits of fission yeasts.
Acs-Szabo L, Papp L, Miklos I Microb Cell. 2024; 11:288-311.
PMID: 39104724 PMC: 11299203. DOI: 10.15698/mic2024.08.833.
Advanced Protocol for Molecular Characterization of Viral Genome in Fission Yeast ().
Zhang J, Benko Z, Zhang C, Zhao R Pathogens. 2024; 13(7).
PMID: 39057793 PMC: 11279667. DOI: 10.3390/pathogens13070566.
Contribution of yeast models to virus research.
Sahaya Glingston R, Yadav J, Rajpoot J, Joshi N, Nagotu S Appl Microbiol Biotechnol. 2021; 105(12):4855-4878.
PMID: 34086116 PMC: 8175935. DOI: 10.1007/s00253-021-11331-w.
Benko Z, Zhang J, Zhao R Curr HIV Res. 2019; 17(6):429-440.
PMID: 31782368 PMC: 9648856. DOI: 10.2174/1570162X17666191128102839.
A fission yeast cell-based system for multidrug resistant HIV-1 proteases.
Benko Z, Liang D, Li G, Elder R, Sarkar A, Takayama J Cell Biosci. 2017; 7:5.
PMID: 28096973 PMC: 5225522. DOI: 10.1186/s13578-016-0131-5.