PRIMARY FACULTY

Joseph John Mattapallil. B.V.Sc., Ph.D.
Assistant Professor
Microbiology and Immunology
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-3737
Fax: 301-295-3773
jmattapalli@usuhs.mil

Research Description: Molecular and cellular mechanisms of HIV pathogenesis, and vaccine development
 
The focus of my laboratory is on understanding the early events in HIV : host interactions to delineate the mechanisms of early pathogenesis, and to use this knowledge to develop better diagnostic, and therapeutic tools. HIV infection is a leading cause of death in the world. According to WHO, almost 45 million people have been infected with HIV. Early HIV host interaction severely cripples the immune system by destroying CD4 T cells that are central to the generation of secondary immune responses to previously encountered pathogens and vaccines (Mattapallil et al Nature 2005, J. Exp. Med. 2006). This damage appears to be most severe in mucosal tissues (oral, gastrointestinal, rectal and vaginal mucosa) as most of the target CD4 T cells reside in these tissues. Not much is known about the early events that drive host-HIV interactions, and the molecular interactions that occur early during the course of infection that leads to the massive replication of the virus. Understanding these early events is the major focus of research in my laboratory, as it will give us new insights into the onset of immunodeficiency and HIV disease progression. We recently showed that mucosal CD4 T cells are highly susceptible to infection (Kader et al J. Virol 2008), and may require novel approaches to protect them from infection and destruction. Other data (Eberly et al J. Immunol 2008) implicates gamma cytokines such as IL-15 in acute viral pathogenesis.
 
We rely on both cellular (12-color flow cytometry), and molecular (quantitative and relative Taqman PCR, micro-array's) tools to address the questions related to HIV and Herpes virus (EBV) infections. Current ongoing work focuses on (1) understanding the role of innate, and adaptive cytokine responses in early host-pathogen interaction and viral amplification, (2) delineating the role of dendritic, and T-regulatory cells in early pathogenesis, (3) understanding the mechanisms for failure of mucosal CD4 T cell repopulation during anti-retroviral therapy, (4) determine the mechanisms that drive reactivation of EBV infection during HIV/AIDS leading to onset of cancer and oral diseases, (5) identifying molecular biomarkers of HIV, and EBV disease progression using microarray and proteomic tools, (6) delineating the role of cellular microRNA in immunity vs early viral pathogenesis, and finally (7) development of vaccines against HIV infection using recombinant vaccine candidates. We use both in vitro approaches, and in vivo infections in non-human primate models such a rhesus macaques. These studies will significantly advance our knowledge about the cellular and molecular mechanisms of viral pathogenesis, and help us develop better therapeutic and vaccine approaches to control HIV, and other related viral infections.

Publications

Kader, M., Hassan, W., Eberly, M., Piatak, M., Lifson, J., Roederer, M & Mattapallil, JJ. 2008. Anti-retroviral therapy prior to acute viral replication preserves CD4 T cells in the periphery but not in the rectal mucosa during acute simian immunodeficiency virus infection. J. Virol. 2008 Sept 3. [Epub ahead of print].
 
Vaccari M, Mattapallil J.J, Song K, Tsai WP, Hryniewicz A, Venzon D, Zanetti M, Reimann KA, Roederer M, Franchini G. 2008. Reduced protection from SIVmac251 afforded by memory CD8+ T-cells induced by vaccination in condition of CD4+ T-cell deficiency. J Virol. 2008 Jul 30. [Epub ahead of print].
 
Mattapallil, JJ* and Roederer M. The mucosa and vaccine induced immune protection in nonhuman primates. 2008. Current Opinion in HIV/AIDS. 3:387-92. (*Corresponding author).
 
Mattapallil MJ, Augello A, Cheadle C, Teichberg D, Becker K, Chan CC, Mattapallil JJ, Pennesi G, Caspi RR. 2008. Differentially expressed genes in MHC-compatible rat strains that are susceptible or resistant to experimental autoimmune uveitis. Invest Ophthalmol Vis Sci 49(5):1957-70.
 
Roederer M and Mattapallil, J.J*. 2007. CCR5 vs HIV: the less the better!. Blood 109 (3): 854. (*Corresponding author).
 
David P. Wilson, Mattapallil, J.J., Lei Zhang, Mario Roederer, Miles P. Davenport1. 2007. Estimating the infectivity of CCR5-tropic SIVmac251 in the gut: implications for HIV vaccination. J. Virol. 81(5): 8025-9.
 
Petrovas C, Price DA, Mattapallil J, Ambrozak DR, Geldmacher C, Cecchinato V, Vaccari M, Tryniszewska E, Gostick E, Roederer M, Douek DC, Morgan SH, Davis SJ, Franchini G, Koup RA. 2007. SIV-specific CD8+T-cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood: 110(3): 928-36.
 
Seggewiss R, Lore K, Guenaga FJ, Pittaluga S, Mattapallil J, Chow CK, Koup RA, Camphausen K, Nason MC, Meier-Schellersheim M, Donahue RE, Blazar BR, Dunbar CE, Douek DC. 2007. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood: 110(1): 441-9.
 
Mattapallil, J. J*., Hill, B., Douek, D.C., and Roederer, M. 2006. Systemic vaccination prevents the total destruction of mucosal CD4 T cells during acute SIV challenge. J. Med. Primatol: 35(4-5): 217-24. (*Corresponding author).
 
Mattapallil, J. J., Douek, D.C., Buckler-White, A., Montefiori, D., Letvin, N. L., Nabel, G. J and Roederer, M. 2006. Vaccination prevents the destruction of CD4 memory T cells during acute SIV infection. J. Exp. Med: 203 (6): 1533-41.
 
Mattapallil, J. J*., and Roederer, M. 2006. HIV Vaccines: can mucosal CD4 T cells be preserved? Current opinion in HIV/AIDS: 1 (4): 272-276. (*Corresponding author).
 
Mattapallil, J. J*., and Roederer, M. 2006. Acute HIV pathogenesis: it takes more than guts. Current opinion in HIV/AIDS: 1 (1): 10-15. (*Corresponding author).
 
Wille, U., Flynn, B. J., Lore, K., Koup, R. A., Miles, A.P., Saul, A., Kedl, R. M., Mattapallil, J. J., Weiss, W.R., Roederer, M and Seder, R. A. 2006. TLR agonists influence the magnitude and quality of Th1 and CD8+ T cell responses following prime-boost immunization in non-human primates. J. Exp. Med: 203: 1249-58.
 
Kuwata, T., Dehghani, H., Plishka, R., Buckler-White, A., Igarashi, T., Mattapallil, J.J., Roederer, M and Hirsch, V. M. 2005. Characterization of Infectious Molecular Clones from a Simian Immunodeficiency Virus-infected Rapid Progressor (RP) Macaque: Differential Selection of RP-Specific Envelope Mutations in vitro and in vivo. J. Virol: 80: 1463-75.
 
Mattapallil, J. J., Douek, D.C., Hill, B., Nishimura, Y., Martin, M.A. and Roederer, M. 2005. Massive infection and loss of memory CD4 T-cells in multiple tissues during acute SIV Infection. Nature: 434: 1093-97.
 
Wille, U., Flynn, B. J., Lore, K., Koup, R. A., Kedl, R. M., Mattapallil, J. J., Nason, M., Roederer, M., Weiss, W. R and Seder, R. A. 2005. HIV Gag protein conjugated to a TLR7/8 agonist elicits Th1 and CD8+ T cell responses in monkeys. PNAS: 102 (42): 15190-4.
 
Nishimura, Y., Brown, C. R., Mattapallil, J. J., Igarashi, T., Buckler-White, A., Lafont, B., Hirsch, V., Roederer, M and Martin, M. A. 2005. Resting naïve CD4+ T cells are massively infected and eliminated by X4-tropic SHIVs in Macaques. PNAS: 102 (22): 8000-5.
 
Song, K., Rabin, R. L., Hill, B. J., De Rosa, S., Perfetto, S. P., Zhang, H. H., Foley, J. F., Reiner, J. S., Liu, J., Mattapallil, J. J., Douek, D. C., Roederer, M and Farber, J. M. 2005. Novel subsets of CD4+ memory T cells reveal early-branched pathways of T cell differentiation in humans. PNAS: 102 (22): 7916-21.
 
Mattapallil, J. J., Letvin, N. L., and Roederer, M. 2004. T cell dynamics in acute SIV infection. AIDS 18 (1): 13-23.
 
Mattapallil, J. J., Reay, E., and Dandekar, S. 2000. Early expansion of CD8ab+ T cells is observed in the intestinal epithelium in contrast to the depletion CD8aa+ T cells during primary simian immunodeficiency virus infection of rhesus macaques. AIDS: 14 (6): 637-46.
 
Mattapallil, J. J., Dandekar, S., Canfield, D. R., and Solnick, J. V. 2000. A predominant Th-1 type of immune response is induced early during acute H.pylori infection in rhesus macaques. Gastroenterology: 118(2): 307-315.
 
Mattapallil, J. J., Smit-McBride, Z., Dailey, P., and Dandekar, S. 1999. Activated memory CD4+ T cells repopulate the intestinal mucosa early after anti-retroviral therapy but exhibit a decreased potential to produce IL-2. J. Virol: 73(8): 6661-9.
 
Mattapallil, J. J., Smit-McBride, Z., and Dandekar, S. 1999. Intestinal epithelium is an early extra-thymic site for the increased prevalence of CD34+ progenitor cells during primary SIV infection. J. Virol: 73(5): 4518-23.
 
Mattapallil, J. J., Smit-McBride, Z., McChesney, M., and Dandekar, S. 1998. Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP-1beta expression and display antiviral cytotoxic activity despite severe CD4 (+) T-cell depletion in primary simian immunodeficiency virus infection. J. Virol: 72(8): 6421-9.
 
Smit-McBride, Z., Mattapallil, J. J., D. A. Ferrick., and Dandekar, S. 1998. Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4 (+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J. Virol: 72(8): 6646-56.
 
Smit-McBride, Z., Mattapallil, J. J., Villinger, F., Ansari, A A and Dandekar, S. 1998. Intracellular cytokine expression in the CD4+ and CD8+ T cells from intestinal mucosa of simian immunodeficiency virus infected macaques. J. Med. Primatol: 27 (2-3): 129-140.
 
B. C. Taylor., Mattapallil, J. J., R. Scibienski and Stott, J. L. 1994. Characterization of a novel bovine cell-cell adhesion protein. Tissue Antigens: 44(4): 252-60.

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