Manoj K. Pastey, DVM, MS, PhD
Assistant Professor, Molecular Virology
Diplomate, American College of Veterinary Microbiologists:
Certified in Veterinary Virology and Veterinary Immunology
American Society for Microbiology
American Society for Virology
American College of Veterinary Microbiologists
American Federation of Medical Research
Indian Veterinary Association
NIH Staff Recognition Award for Research Excellence, Vaccine Research Center, NIH, 2004.
NIH Fellows Award for Research Excellence in Biomedical Research, NIH, 2004.
Sidney P. Colowick Award for Outstanding Postdoctoral Fellow in the Dept. of Microbiology & Immunology, Vanderbilt University, Nashville, TN, 2000.
Henry Christian Award for Excellence in Research presented at Experimental Biology Meeting (FASEB), Washington DC, 1999.
Trainee Travel Award Presented at Experimental Biology Meeting (FASEB), Washington DC, 1999.
Travel Grant Award presented at 12th annual meeting of American Society for Virology, 1993.
Graduate Research Assistantship from University of Maryland, College Park, MD, 1989-1996.
PhD 1996 Molecular Virology U of Maryland, College Park, Maryland
MS 1991 Molecular Virology U of Maryland, College Park, Maryland
BVSc 1988 Veterinary Medicine U of
Agricultural Sciences, Bangalore, India
Indian Veterinary Research Institute Junior Merit Scholarship, 1988-1989.
University of Agricultural Sciences Merit Scholarship, 1983-1988.
University of Agricultural Sciences 7 Gold Medals for Securing First Rank in Undergraduate Studies, 1983-1988.
Karnataka State Government Youth Services & Sports Award for Academic Excellence in Undergraduate Studies.
The laboratory of Dr. Pastey works in the molecular biology and pathogenesis of HIV-1 and RSV.
Human Immunodeficiency virus is the primary cause of acquired immunodeficiency syndrome (AIDS) worldwide. HIV belongs to the retrovirus family of viruses, whose members share a unique method of replicating themselves when they infect living cells. HIV infection of host cells is initiated by virus attachment, fusion of the viral and cellular membrane and entry of the viral core into the cytoplasm. HIV encounters blocks in the target cells by innate cellular resistance at various stages of HIV lifecycle. One of the many viral strategies to counteract host cell restriction is to produce a protein that blocks the restrictive factor. We have identified a potentially new HIV protein produced from an alternative reading frame of the HIV genome that is essential for replication of HIV in human peripheral blood mononuclear cells (PBMCs), some T cell lines and HeLa T4 cells. By mutating the open reading frame of the new protein, we show that HIV replication is restricted in PBMCs and T cell lines, but the virus can grow in cell lines derived from undifferentiated neuroblastoma or osteoblastoma such as U87 and Ghost Cells. The new protein is highly conserved in all clades of HIV. Our laboratory is interested in further characterizing the protein and defining its biological relevance in HIV replication. In addition, we are also interested in identifying the potential host cell restrictive factor that may play a role in blocking HIV replication that is overcome by the new HIV protein.
Human respiratory syncytial virus belongs to the Pneumovirus genus of the Paramyxoviridae family. RSV is the major cause of acute lower respiratory tract illness in infants and young children. The RSV envelope contains two major glycoproteins, the G (attachment) and the F (fusion) glycoproteins. The F glycoprotein mediates at least two essential steps in the viral life cycle that requires membrane fusion: it promotes fusion of the viral and cellular membranes with subsequent transfer of viral genome material into the cell, and it promotes fusion of the infected cell membrane with those of adjacent cell membranes, leading to syncytia formation. Our previous work has shown that the RSV F protein interacts with a cellular protein, RhoA and facilitates virus-induced syncytium formation. In addition, a RhoA-derived peptide inhibits syncytium formation induced by RSV and parainfluenza virus type-3 (Nature Medicine (2000) 6, 35-40). RhoA signaling is also important for budding of filamentous form of RSV. One of the goals of the project is to study the determinants of RSV morphological forms that may influence pathogenesis, and provide the basis for new anti-viral approaches.
Another goal of the RSV projects is to study the interaction of RSV matrix (M) protein with the cellular proteins. Previously published reports have shown that matrix protein of HIV-1, ebola and equine infectious anemia virus interacts with cellular adaptor protein (present in clathrin-coated vesicles) and helps in the release of virus from the cell. Our laboratory is interested in finding whether the M protein interacts with adaptor protein or other cellular proteins that may help in the release of RSV from the surface of the cells. The interaction between RSV matrix and adaptor protein or other cellular proteins can be a new target for developing drugs that block the interaction and thus prevent the release of new budding virus.
Pastey, M.K. and Samal, S.K. (1993). Structure and sequence comparison of bovine respiratory syncytial virus fusion protein. Virus Research, 29:195-202.
Samal, S.K., Pastey, M.K., Carmel, D.K. and Mohanty, S.B. (1993). Reliable confirmation of antibodies to bovine respiratory syncytial virus (BRSV) with an enzyme linked immunosorbent assay using BRSV nucleocapsid protein expressed in insect cells.Journal of Clinical Microbiology, Vol. 31, No. 12: 3147-3152.
Samal, S.K., Pastey, M.K., and Mohanty, S.B. (1993). Bovine respiratory syncytial virus nucleocapsid protein expressed in insect cells specifically interacts with the phosphoprotein and the M2 protein. Virology, 193: 470-473.
Samal, S.K and Pastey, M.K. (1994). Bovine respiratory syncytial virus genes in immune recognition and pathogenesis. Proceedings of the International Symposium on Virus-cell Interaction. 2:159-162.
Pastey, M.K. and Samal, S.K. (1995). Nucleotide sequence analysis of the non-structural NS1 (1C) and NS2 (1B) protein genes of bovine respiratory syncytial virus. Journal of General Virology, 76:193-197.
Samal, S.K and Pastey, M.K. (1997). Role of envelope glycoproteins of bovine respiratory syncytial virus in cell fusion. Indian Journal of Biochemistry and Biophysics, 34:181-185.
Pastey, M.K. and Samal, S.K. (1997). Analysis of the bovine respiratory syncytial virus fusion protein using monoclonal antibodies. Veterinary Microbiology, 58, Issue 2-4:175-185.
Pastey, M.K. and Samal, S.K. (1997). Analysis of bovine respiratory syncytial virus envelope glycoproteins in cell fusion. Journal of General Virology, 78:1885-1889.
Pastey, M.K. and Samal, S.K. (1997). Role of individual N-linked oligosaccharide chains and different regions of bovine respiratory syncytial virus fusion protein in cell surface transport. Archives of Virology, 142: 2309-2320.
Pastey, M.K. and Samal, S.K. (1998). Baculovirus expression of the fusion protein gene of bovine respiratory syncytial virus and utility of the recombinant protein in a diagnostic enzyme immunoassay. Journal of Clinical Microbiology, 35:1105-1108.
Yunus, A.S., Krishnamurthy, S., Pastey, M.K., Huang, Z., Khattar, S., Collins, P.L and Samal, S.K. (1999). Rescue of a bovine respiratory syncytial virus genomic RNA analog by bovine, human and ovine respiratory syncytial viruses confirms the "functional integrity" and "cross-recognition" of BRSV cis-acting elements by HRSV and ORSV. Archives of Virology, 144:1977-1990.
Pastey, M.K., Crowe, J.E and Graham, B.S. (1999). RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation. Journal of Virology, 73: 7262-7270.
Pastey, M.K., Gower, T.L., Spearman, P.W., Crowe, J.E and Graham, B.S. (2000). A RhoA-derived peptide inhibits respiratory syncytial virus and parainfluenza virus type-3-induced syncytium formation. Nature Medicine, 6: 35-40.
Pastey, M.K., Gower, T.L., Peeples, M., Collins, P.L., Hart, T.K., Guth, A and Graham, B.S. (2004). RhoA signaling is required for respiratory syncytial virus-induced syncytia formation and filamentous virion morphology. (in Press, Journal of Virology).
Pastey, M.K., Huang, Y., Nabel, A. and Graham, B.S. (2004). SARS coronavirus buds from lipid raft microdomains. (submitted to Journal of Virology).
Pastey, M.K. and Graham, B.S. (2004). Morphometrics of respiratory syncytial virus. (submitted to Journal of Virology).