DR. ANIL KUMAR
ANIL KUMAR, Ph.D.
Department of Microbiology
Ponce School of Medicine
Ponce, PR 00732
Phone (787) 840-2575 ext 2215
(787) 840-3010 Direct line
Fax (775) 659-7298
Year
1978
1980
1987
1994-1995
1995-1997
Granting Institutions
Lucknow University, India
Lucknow University,India
Kanpur University, India
Institute Gustave Roussy, France
University of Birmingham, Italy
B.Sc.
M.Sc.
Ph.D.
Post-Doc
Post-Doc
Subjects
Zoology, Botany, Chemistry
Zoology
Chemotherapy and Immunology of MalariaDegree awarded in Zoology
Molecular Immunology
Cellular Immunology
RESEARCH INTERESTS (Anil Kumar, Ph.D.)
We are involved in the following projects. First two are funded from NIH through RO-1 and MBRS Mechanism. Project no.3 was submitted as RO-1 application to NIH. This has received a priority score of 185. We are not sure if we will be able to secure the funding for this project, therefore we are in the process of revising the application. Project number 4 was submitted as R-21 application and it received a priority score of 220. We have revised this application and submitted to NIH for reconsideration. Below is abstract of the four projects. I hope that this will give you idea of my research interests.
Project number-1 (5R01DA015013-04)
Approximately 30 percent of HIV-positive patients have a history of injection drug abuse that frequently involves the use of opiates. Because of the substantial evidence that both endogenous and exogenous opioids and opiate-abuse modulate immune function, and also that opiates augment HIV-1 replication in vitro, there continues to be a extended debate and considerable research has been aimed at understanding whether opiates alter HIV-1 infection and progression to AIDS. The present application is designed to address this important question in SHIV KU- 2/macaque model of AIDS. This model of HIV/AIDS has been successfully used in our laboratory to study the pathogenesis of the virus, effect of anti retroviral drugs and evaluation of different candidate vaccines. We will use morphine sulfate to establish opiate-dependence in macaques by intramuscular injection, and infect these macaques along with control animals with highly pathogenic SHIV KU-2. These experiments will determine, whether morphine treatment alters the expression of mu-opioid receptor (MOR) in monkeys, and whether morphine- dependence enhances intensity of SHIV KU-2 replication in vivo and accelerates the onset of clinical disease in SHIV/macaque model of HIV/AIDS. We will also examine the effect of morphine treatment on in vivo apoptosis of T cells. In another series of experiments we will examine the effect of morphine addiction on the development and persistence of virus-specific immune responses that will help us understand effect of drug-abuse on the development of immune responses, induced by a vaccine. We will immunize morphine-dependent and control macaques with a live virus vaccine that has been shown to confer solid protection against SHIV-induced AIDS. The virus-specific immune response in these two groups will be compared for the strength and duration. These animals will be challenged with pathogenic SHIV KU-2 to determine whether morphine-dependence compromises the live vaccine-induced protection.
Project number-2 (3S06 GM008239-18S2)
The problem of HIV epidemic has not only affected the third world countries in Asia and Africa but also has had serious impact on the economy of developed countries like United States and Puerto Rico. Due to the lack of availability of a HIV vaccine, it has become increasingly important to develop alternate strategies for the management of this disease. The introduction of HAART 6 years ago has resulted in a dramatic reversal in disease progression for those with access to this drug cocktail. However, the high cost associated with the cocktail has prevented individuals from the Caribbean and Third World countries to realize a complete effect of HAART. Even in developed countries where the cost is not an issue, other problems like adherence, drug resistance and drug-associated toxicity have limited the long-term use of these drugs. Recently introduced structure treatment interruptions have offered a glimpse of hope for these individuals. However limited clinical trials have failed to provide a concrete evidence regarding utility of this approach. We will test utility of the structured treatment in SHIV/macaque model of HIV/AIDS. We will infect rhesus macaques with a pathogenic SHIV and compare different virological and immunological responses in two groups; macaques those are treated with continuous antiretroviral treatment with those macaques receiving structured treatment. Specific Aims of this application are (i) To identify whether a short-term structured treatment in SHIV-infected macaques will suppress long-term virus replication, and if it does, determine the immune correlates of suppression, and (ii) To identify if the rebounding viruses in treated groups are PMPA-resistant, and if so, characterize the mutation in the Reverse Transcriptase gene (RT) of the virus.
Project number-3 (1R01AA015045 )
Alcohol abuse and its related consequences together with HIV/AIDS are the major health problems in many parts of the world. Chronic alcohol use has been found to impair various immune functions, thereby making the body more susceptible to invading pathogens. Based on the several studies in the literature that alcohol consumption leads to immunological deterioration, we hypothesize that alcohol use may exacerbate HIV infection and also accelerate the onset of clinical disease. This is a complex research issue and, to date, there are no clear answers in this regard. The prospect of testing proof-of-concept studies regarding correlation between alcohol consumption and disease in HIV-positive humans is untenable because of variable incubation periods and long length time that are required to address this important issue. Furthermore it is not known whether alcohol abuse will adversely affect the vaccine-induced immune response and it will confer inferior protection after natural infection. The latter issue becomes more important because several HIV candidate vaccine are in various phase of clinical trial. The present application is designed to address these vital questions in SHIVKU/macaque model of AIDS. This model of HIV/AIDS has been successfully used in our laboratory to study the pathogenesis of the virus, effect of anti retroviral drugs and evaluation of different candidate vaccines. In this proposal we will test the hypotheses in four specific aims. The experiments in Aim-1 will examine the effect of alcohol on co-receptor expression and replication of SIV and SHIV(s). We will also examine the effect of alcohol on NFkb activation, and whether suppressing NFkb activation can modulate virus replication. The proposed experiments in Aim-2 deal with establishment of a SHIV/macaque model of alcohol dependence and examine whether alcohol consumption accelerates the onset of SHIV-induced AIDS in macaques. In Aim 3 and 4, we will examine the effect of chronic alcohol consumption on development and persistence of a live attenuated vaccine-induced immune responses and whether challenge with a pathogenic SHIV confers inferior protection in alcohol-dependent macaques. These studies will help us not only to understand pathogenesis of the SHIVKU in alcohol abuse set-up, but also whether chronic alcohol abuse compromises vaccine-induced development and persistence of virus-specific immune responses and vaccine mediated protection after pathogenic challenge.
Project number-4
Dengue virus (DV), a positive stranded RNA virus, is transmitted by the mosquitoes, and is the cause of a growing public health problem. Approximately 60-80 million persons are infected annually, and rates of infection are as high as 6% in some areas. The virus can be divided into 4 serotypes (DEN 1-4), and all 4 serotypes circulate in Caribbean, Asia and the Americas. Infection with one strain does not provide protective immunity against other strains. There are several reasons for the lack of an effective vaccine against DV. It is known that pre-existing non neutralizing antibodies indeed enhance the virus replication during secondary infection. In view of this an ideal vaccine will include only protective epitopes so that deleterious effect can be avoided. However idea of construction of a polyepitope vaccine cannot be realized at this time because adequate numbers of immune targets have not been identified in all 4 serotypes. This application deals with identification of such targets but our proposal remains limited to T cell epitopes. We plan to identify CTL and/or T-helper epitopes in prM-E and NS-1 protein of the DEN-3. Our central hypothesis is that prM-E and NS-1 protein are targets of T cell mediated immune response during natural infection with DEN-3, and there are T-helper and CTL epitopes in these proteins. We will develop DV3-specific T cell lines and clones. These clones will be characterized for CD4 and CD8 phenotype and used for the identification of T-helper and CTL epitopes in ELISPOT assays. The clones will be first tested against overlapping peptides encompassing full length prM-E and NS1, followed by screening against deletion peptides. The HLA restriction element for the newly identified epitopes will be determined. We will also determine functional properties of the CD4 and CD8 T cell clones like cytokine secretion pattern, ability to block/reduce replication of DEN-3 as well as other serotypes.
GRANTS
Current:
7 RO1 DA 0115013-02, NIDA, NIH 09-19-2001-02-28-2006
Effects of opiate on virus/host responses in SHIV/macaque
Role on Grant- Principal-investigator
SO6 GM008239-18S2, 06-01-03 to 05-31-05
Structured Antiretroviral Treatment in SHIV/Macaques
Role on Grant- Principal Investigator
1 RO1 AA015045 07-05-04 to 03-31-09
Alcohol and AIDS: Pathogenesis and Immunity in macaque
Role on Grant- Principal Investigator
R21 AI059361-01A1 2005-2007
Immune Targets during natural dengue infection
Role on Grant- Principal Investigator
Research Publications:
S. Buch, F. Villinger, D. Pinson, Y. Hou, I. Adany, Z. Li, R. Raghavan, Anil Kumar and O. Narayan (2002). Innate differences between simian human immunodeficiency virus (SHIVKU-2) infected rhesus and pig-tailed macaques in development of neurological disease. Virology 295:54-62.
Anil Kumar, S Mukherjee, J Shen, S Buch, Z Li, I Adany, Z Liu, W Zhuge, M Piatak, J lifson, H. McClure and O Narayan (2002) Immunization of mavcaques with live SHIV vaccines conferred long-term protection and sterilizing immunity against mucosally inoculated homologous and heterologous challenge viruses. Virology 301:189-205.
Andrey Hicks, R.Potula, Y Sui, F Villinger, D Pinson, I Adany, Z Li, C Long, P Cheney, J Marcario, F Novembre, N Mueller, Anil Kumar, E Major, O Narayan and S Buch (2002) Neuropathogenesis of Lentiviral Infection in Macaques: Roles of CXCR4 and CCR5 viruses and IL-4 in Enhancing MCP-1 Production in Macrophages. Am J. Pathol. 161:813-822.
Anil Kumar (2003). Tenofovir disoproxil fumarate. Drugs. 63:1609-1610.
Richard J. Noel, Suman Chaudhary, Nayra Rodriguez, Anil Kumar and Yasuhiro Yamamura (2003). Phylogenetic relationship between Puerto Rico and Continental USA HIV-1 pol sequences: A shared HIV-1 infection. Cellular and Molecular Biology 49:1193-1198.
Martin D. Hill, Eric Lorenzo and Anil Kumar (2004). Changes in the human immunodeficiency virus V3 region that correspond with disease progression. Virus Research, 106:27-33.
Grissell Tirado, Gloria Jove, Richard J. Noel, Rakesh Kumar, E. Reyes, G. Sepulveda, Y. Yamamura and Anil Kumar (2004). Differential virus evolution in blood and genital tract of HIV-infected females: Evidence for the involvement of drug and non-drug resistance-associated mutations. Virology, 324:577-586.
Grissell Tirado, Gloria Jove, Rakesh Kumar, Richard J. Noel, E. Reyes, G. Sepulveda, Y. Yamamura and Anil Kumar (2004). Compartmentalization of Drug Resistant-Associated Mutations in Treatment Naïve HIV-infected Female. AIDS Research and Human Retroviruses, 20: 682-684.
Rakesh Kumar, Cynthia Torres, Yasuhiro Yamamura, Idia Rodriguez, Melween Martinez, Silvija Staprans, Robert M. Donahoe, Edmundo Kraiselburd, Edward B. Stephens and Anil Kumar. 2004. Modulation of Viral Set Point by Morphine in Rhesus Macaques Infected with SIV and SHIV. Journal of Virology. 78:11425-11428.
Eric Lorenzo, Rakesh Kumar, Martin D. Hill, Sonia Costas, Suman Chaudhary, Grissell Tirado, Yashuhiro Yamamura and Anil Kumar. 2004. Genetic Characterization of Human Immunodeficiency Virus type 1 Tat before and after Highly Active Antiretroviral Therapy. AIDS Research and Human Retroviruses. 20:1108-1112.
Eric Lorenzo, Maria C. Colon, Sharilyn Almodovar, Irvin M. Maldonado, Sandra Gonzalez, Sonia E. Costa, Martin D. Hill, Rafael Mendoza, Gladys Sepulveda, Richard Yanagihara, Vivek Nerurkar, Rakesh Kumar, Yasuhiro Yamamura, Walter A. Scott and Anil Kumar. 2004. Influence of CD4 T Cell Counts on Viral Evolution in HIV-1 Infected Individuals Undergoing Suppressive HAART . Virology, 330:116-126.
Grissell Tirado, Gloria Jove, E. Reyes, G. Sepulveda, Y. Yamamura, D.P. Singh and Anil Kumar. 2005. Differential evolution of cell-associated virus in blood and genital tract of HIV-infected females undergoing HAART. Virology, in press.
Yashuhiro Yamamura, Suman Chaudhary, Nayra Rodríguez, Richard J. Noel, Santiago Collado, Jhoanne Munoz, D.P. Singh and Anil Kumar 2005. Correlation between CD4 T cell Counts and Virus Compartmentalization in Genital and Systemic Compartments of HIV-infected Females. Ms. submitted.
Rakesh Kumar, Antonio E. Perez-Casanova, Grissell Tirado, Cynthia Torres, Yasuhiro Yamamura, Idia Rodriguez, Melween Martinez, Silvija Staprans, J. Dee Higley and Anil Kumar. 2005. Increased viral replication in SIV/SHIV-infected macaques with self-administering model of chronic alcohol consumption. Ms. submitted.
Teaching:
I have been involved in teaching virology to medical and graduate students. I also facilitate Problem Based Learning (PBL) for 1 st and 2 nd year Medical students. I have also been involved in training of several graduate students, post-doctoral fellows and technicians.
