Phalguni Gupta, PhD
Infectious Disease & Microbiology
130 DeSoto Street
Pittsburgh, Pennsylvania 15261
Phone: (412) 624-7998
Dr. Gupta is a Professor in the Department of Infectious Diseases and Microbiology at the University of Pittsburgh, School of Public Health. He received his Ph.D. in Biochemistry in 1972 from the University of Wisconsin. His research interest focused on the development of an effective mucosal AIDS vaccine. He is using bacterial delivery system to stimulate the gut-associated immune responses to enhance immunity against HIV infection.
A novel Clostridia perfringens based oral vaccine is being developed to induce mucosal immunity against HIV and SIV. We have constructed a non-cytotoxic C. perfringens expressing large amount of HIV p24 and SIV p27 proteins in the form of inclusion bodies. When they are orally administered into mouse and rats these proteins were detected in the terminal ileum region of the small intestines. Furthermore, dendritic cells beneath the mucosal surface in the Peyer’s Patches(PPs) captured both HIV and SIV antigens when mouse PPs were exposed to recombinant expressing HIV and SIV antigens in the lumen. In addition, mice orally fed recombinant C. perfringens expressing SIV p27 mixed with mLT R192G showed an SIV p27 specific IgA response in feces and in the vagina. In an ongoing study we are constructing C. perfringens expressing HIV and SIV reverse transcriptase (RT) and envelop gp120 proteins and measure mocosal and systemic immune responses to HIV and SIV proteins expressed in C. perfringens in mouse. The proposed vaccine strategy holds a great promise for developing a practical vaccine against HIV due to its safety, low cost to produce and easy to administer.
A novel in vitro cervical tissue based organ culture has been developed to study heterosexual transmission of HIV-1. This model system allows the maintenance of the natural architecture of the tissue in the organ culture as evidenced by histology and quantitative immnostaining of immune and non-immune cellular proteins. Infectious virus is found to be transmitted from cell-free as well as cell-associated HIV-1 across the mucosal barrier. Using simultaneous in situ hybridization and immunophenotyping techniques, HIV-1 expressing cells are detected to the basal layer of the epithelium and identified as being activated CD4+ T lymphocytes and CD14+ macrophages. The model is being used in elucidating viral and cellular factors that are involved in heterosexual transmission of HIV-1. In addition, this organ culture is being used to develop and test microbicides for their anti-HIV activity.
Studies are being done to investigate the origin and dynamics of HIV in semen. This has demonstrated presence of high levels of HIV in semen of infected subjects at all stages of the disease, but in most subjects HIV present in semen is different than those present in blood. Our recent studies indicate that HIV shedding is highly dynamic and it could influence the compartmentalization of HIV between semen and blood. Studies are underway to determine the tissue origin of HIV in semen by comparing sequences of HIV in semen and male genital organ tissues. Studies are also going on to determine the dynamics of HIV in semen as compared to that in blood and to determine the viral reservoir in semen following antiretroviral therapy. In addition, studies are being done to elucidate the mechanism of sexual transmission of HIV-1.
Our laboratory is also involved in International study of HIV infection in India. Our previous genetic studies of HIV-1 circulating at different parts of India indicate that the subtype C predominates in India with a small proportion of infection caused by subtype A or B. Studies are being conducted to investigate the mechanism for this asymmetric distribution of HIV subtypes in India. Three mechanisms are being investigated: 1) enhanced replication fitness of type C subtypes, 2) higher transmission efficiency of type C subtypes and 3) Founder effect: unique characteristics of founder virus resulting in disproportionate spread of subtype C viruses. Sequence analysis, organ culture and replication fitness methods are being used to investigate these possibilities.
A number of studies are being conducted to investigate the mechanism of nonlytic CD8+ T cell mediated suppression of HIV and SIV at the cellular and molecular level, and to determine its role in HIV and SIV pathogenesis.
- Ding M, Bullotta A, Caruso L, Gupta P, Rinaldo CR, Chen Y. An optimized sensitive method for quantitation of DNA/RNA viruses in heparinized and cyropreserved plasma. J Virol Methods. 2011 May 17. [Epub ahead of print]
- Shen C, Ding M, Craigo JK, Tarwater P, Chatterjee R, Roy P, Guha SK, Saha B, Modak D, Neogi D, Chen Y, Gupta P. Genetic characterization of HIV-1 from semen and blood from clade C-infected subjects from India and effect of therapy in these body compartments. Virology. 2010 Jun 5;401(2):190-6. Epub 2010 Mar 15. PMID:20231027
- Helmus RA, Poonam P, Caruso L, Gupta P, Chen Y. Induction of SIV p27-specific multifunctional T cells in the gut following prime-boost immunization with Clostridium perfringens and adenovirus vaccines expressing SIV p27. Curr HIV Res. 2010 Mar;8(2):101-12. PMID:20163344
- Chakrabarti AK, Caruso L, Ding M, Shen C, Buchanan W, Gupta P, Rinaldo CR, Chen Y. Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy. AIDS Res Ther. 2009 Oct 2;6:20. PMID:19799780
- Richardson-Harman N, Lackman-Smith C, Fletcher PS, Anton PA, Bremer JW, Dezzutti CS, Elliott J, Grivel JC, Guenthner P, Gupta P, Jones M, Lurain NS, Margolis LB, Mohan S, Ratner D, Reichelderfer P, Roberts P, Shattock RJ, Cummins JE Jr. Multisite comparison of anti-human immunodeficiency virus microbicide activity in explant assays using a novel endpoint analysis. J Clin Microbiol. 2009 Nov;47(11):3530-9. Epub 2009 Sep 2. PMID:19726602
- Tumne A, Prasad VS, Chen Y, Stolz DB, Saha K, Ratner DM, Ding M, Watkins SC, Gupta P. Noncytotoxic suppression of human immunodeficiency virus type 1 transcription by exosomes secreted from CD8+ T cells. J Virol. 2009 May;83(9):4354-64. Epub 2009 Feb 4. PMID:19193788
- Rodriguez MA, Ding M, Ratner D, Chen Y, Tripathy SP, Kulkarni SS, Chatterjee R, Tarwater PM, Gupta P. High replication fitness and transmission efficiency of HIV-1 subtype C from India: Implications for subtype C predominance. Virology. 2009 Mar 15;385(2):416-24. Epub 2009 Jan 20. PMID:19157481
- Ding M, Tarwater P, Rodriguez M, Chatterjee R, Ratner D, Yamamura Y, Roy P, Mellors J, Neogi D, Chen Y, Gupta P. Estimation of the predictive role of plasma viral load on CD4 decline in HIV-1 subtype C-infected subjects in India. J Acquir Immune Defic Syndr. 2009 Feb 1;50(2):119-25. PMID:19131898
- Chen Y, Shen C, Wu H, Caruso L, Ratner D, Rodriguez M, Chen X, Gupta P. Biological properties of HIV-1 subtype B' isolates from infected Chinese blood donors at different disease stages. Virology. 2009 Feb 5;384(1):161-8. Epub 2008 Dec 6. PMID:19058828
- Gupta P, Chen Y. Chromosomal engineering of Clostridium perfringens using group II introns. Methods Mol Biol. 2008;435:217-28. PMID:18370079