Faculty Profile

Montefiore Einstein Home
Albert Einstein College of Medicine
Faculty Directory
Vinayaka R. Prasad, Ph.D.

Vinayaka R. Prasad, Ph.D.

Professor, Department of Microbiology & Immunology

Area of Research: Role of extrinsic factors such as CCL2 in the modulation of ESCRT factors to enhance HIV-1 budding and release; Effect of drugs of abuse on HIV replication and HAND; Viral determinants of HIV associated neurocognitive disorders (HAND)

Contact Information

718.430.2517vinayaka.prasad@einsteinmed.edu

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room 705
Bronx, NY 10461

Research Profiles PubMed Portal

More Resources: TWiV 567- PodcastEinstein International AIDS research program

Is this your profile? Edit profile

Professional Interests

Research in our laboratory is focused on two areas of HIV/AIDS: how beta chemokines modulate ESCRT proteins to augment HIV-1 replication and the viral determinants of HIV associated neurocognitive disorders (HAND).

HIV-1 budding, a novel target for therapeutics: We have reported, for the first time, an external stimulus that enhances ESCRT complex-mediated budding and release of HIV-1 from the infected cells. We show that the mechanism by which the  chemokine, CCL2, enhances virus production is by mobilizing ALIX, a key adapter protein of the ESCRT complex III from the cellular actin cytoskeleton to the sites of virus budding and release. ESCRT complexes are essential for the membrane scission step in the bud neck of viruses. We show that CCL2, which is induced upon HIV-1 infection of macrophages, stimulates the budding and release of HIV-1 clade B (HIV-1B), but not that of HIV-1 clade C (HIV-1C), which does not induce CCL2. We also show that immunodepletion of CCL2 strongly inhibits (10-fold) virus production from macrophages. We have shown that the ability to respond to CCL2 levels is dependent on the presence of late motif 2 or LYPX in HIV-1 Gag, which recruits ALIX to facilitate virion budding. We show that clade C viruses have a highly conserved absence of the LY dipeptide. We also show that the absence of LY contributes to reduced replication fitness of HIV-1C. Interestingly, variants of clade C HIV-1 in India and Africa that have acquired increased replication fitness display novel tetrapeptide insertions in Gag-p6 precisely where the LY dipeptide is missing. These viruses have regained the ability to bind ALIX, are more fit and respond to CCL2.

The lab is currently beginning a study of naturally occurring polymorphisms in ccr2 or ccl2 genes that are known to affect HIV-1 disease. A V64I mutation in ccr2 gene is known to delay HIV disease progression by up to 4 years and an enhancer mutation in ccl2 is known to enhance plasma CCL2 levels and is preferentially enriched in HIV-infected individuals. We are studying the effect of each of these mutations on the CCL2-mediated ALIX mobilization and HIV-1 budding/release and viral fitness.

HIV associated Neurocognitive Disorders (HAND): The severe form of HAND, the HIV associated dementia (HAD), is common among clade-B HIV-infected individuals in the US, but less common among individuals infected with clade-C HIV-1 in India, suggesting clade-specific differences in neuropathogenicity. Understanding clade-specific determinants of neuropathogenesis may shed light on the disease mechanism and help develop targeted drugs for HAD. We previously demonstrated that due to a C31S polymorphism, clade C Tat lacks the chemokine function of Clade B Tat that plays a crucial role in an increased brain infiltration of monocytic phagocytes in HAD. We studied neuropathogenesis induced by two HIV-1 clades B and C using SCID mouse HIV encephalitis (SCID-HIVE) model and reported that while the introduction of clade B HIV-1ADA into SCID mouse brain recapitulates the key features of human HAD disease, mice exposed to similar inputs of HIVIndie-C1 (clade C) made fewer memory errors than those exposed to HIV-1ADA (clade B). HIV-1ADA also caused greater astrogliosis and loss of neuronal network integrity.

Work from many groups has shown that clade C HIV-1 in Southern Africa can induce HAD at much higher incidence than in India. We hypothesized that such variation is due to polymorphism in the neuropathogenesis determinants in Tat or gp120, the two major neurotoxicity determinants of HAND. With respect to Tat, we observed that the percentage of HIV isolates with dicysteine motif in Tat is 2-3% on the Indian subcontinent while in the Southern African countries, they ranged from 19-26%. These data broadly correlate with the HAD frequencies reported from India, South Africa and Botswana (3-4%, 25% and 38% respectively). This finding has been corroborated using a Zambian HIV-1C isolate that displays a C31 residue and thus an intact dicysteine motif. Our in vitro and SCID-HIVE results clearly indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat.

Since Tat is not the only neurovirulence determinant in HIV-1, we examined whether gp120 exhibits intra-clade differences between India and Southern Africa. Our findings indicate that gp120 can also display region-specific differences. For example, the Southern African HIV isolates appear to contain more robust neurovirulence determinants than those in the Indian isolates. Thus, two different viral genes in India appear to show determinants of low neurotoxicity. These results suggest that clinical studies studying the incidence of HAD or HAND to correlate viral genetic differences must examine both Tat and gp120. Ongoing work in our laboratory is attempting to identify the neurovirulence signatures of gp120 in clade C and clade B virus isolates and exploring the role of exosomes in neurovirulence.

Selected Publications

HIV-1 budding, a novel target for therapeutics

David Ajasin, Vasudev R. Rao, Xuhong Wu, Santhamani Ramasamy, Mario Pujato, Arthur P. Ruiz, Andras Fiser, Anne Bresnick, Ganjam V. Kalpana and Vinayaka R. Prasad (2019) CCL2 Mobilizes ALIX to Facilitate Gag-p6 Mediated HIV-1 Virion Release. eLIFE 2019;8:e35546 doi: 10.7554/eLIFE.35546.

HIV Neuropathogenesis

Arthur P. Ruiz, David Ajasin, Santhamani Ramasamy, Eliseo Eugenin and Vinayaka R. Prasad (2019) A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation. Scientific Reports 9:3308

Rao, V., Neogi, U., Talboom, J. S., Padilla, L., Rahman, M., Fritz-French, C, Gonzalez-Ramirez, Verma, A., Wood, C., Ruprecht, R. M., Ranga, U., Azim, T., Joska, John, Eugenin, T., Shet, A., Bimonte-Nelson, Tyor, W. R. and Prasad, V. R. (2013) Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence. Retrovirology 10:61. DOI: 10.1186/1742-4690-10-61.

Rao, V. R., Sas, A., Eugenin, E., Siddappa, N. B., Bimonte-Nelson, H., Berman, J., Ranga, U., Tyor, W. R. and Prasad, V. R. (2008) HIV-1 clade-specific differences in the induction of neuropathogenesis. J. Neurosci. 28:10010-6.

Quick Links

Faculty Profile

Vinayaka R. Prasad, Ph.D.

Contact Information

Professional Interests

Selected Publications

HIV-1 budding, a novel target for therapeutics

HIV Neuropathogenesis

Related News

News Release

Albert Einstein College of Medicine Receives $11.3M NIH Grant to Expand the Einstein-Rockefeller-CUNY Center for AIDS Research

Research Brief

Chemokines as Drug Target for HIV-1

Research Brief

New Drug Target for HIV-1