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Faculty & Research

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Janice Clements

Department Affiliation Primary: Division of Comparitive Medicine
Secondary: Molecular Biology & Genetics
RankProfessor and Vice Dean for Faculty
Phone Numbers410-955-9770
Lab: 410-955-9821
Emailjclement@jhmi.edu
School of Medicine Address733 North Broadway
839 BRB
Baltimore MD 21205
Link to Lab Homepage
Janice Clements

Research Topic: Molecular Pathogenesis and Latency of SIV & HIV

Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, the simian immunodeficiency virus (SIV) is used to examine the molecular basis for the pathogenesis of HIV CNS disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. Further studies of lentivirus infections of macrophages and specific viral pathogenesis in the central nervous system and the lung are of interest. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease. The SIV Envelope gene and the NEF gene both play important roles in infection of the CNS. The mechanisms of the action of these proteins in the CNS are complex and are under investigation.
 

Her group was the first to identify the role of CD4-independent virus entry in the pathogenesis of neurological disease. They have shown that neurovirulent SIV can infect cells in a CD4-independent, CCR5-dependent manner in primary CNS endothelial cells and cell lines that express only CCR5. Furthermore, studies have shown that the Nef protein from the neurovirulent virus interacts with different cellular kinases than the Nef protein from other strains of SIV. Their studies have demonstrated that replication of neurovirulent virus in vivo by quantitation of viral RNA copies in the brain and viral load in cerebral spinal fluid is directly correlated with the development of CNS lesions during SIV infection. Finally, they have shown that virus replication in the CNS is independently regulated from the peripheral blood. Because virus replication in the brain is mainly in macrophages while in the peripheral blood it occurs in lymphocytes, control of viral replication by innate immune responses in the brain is significant. Current research is examining the role of these innate immune responses on restricting viral RNA transcription and gene expression.

Publications:

Witwer, KW, Sisk, JM, Gama L, and CLEMENTS, JE. MicroRNA Regulation of IFN protein expression: Rapid and sensitive modulation of the Innate Immune Response. J. Immunology, 184(5):2369-76, 2010.
PubMed Ref

Szeto, GL, Brice, AK, Hung-Chih Yang, H-C MD, Barber, SA, Siliciano, RF, CLEMENTS, JE. Minocycline attenuates HIV-1 infection and reactivation by suppressing cellular activation In human CD4+ T cells. J Infect Dis. 2010 Apr 15;201(8):1132-40.
PubMed Ref

Dinoso, JB, Alireza Rabi, S, Blankson, JN, Gama, L., Mankowski, JL, Siliciano, RF, Zink, MC and CLEMENTS, JE. A SIV-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J. Virol.; 83(18):9247-57, 2009.
PubMed Ref

Witwer, KW, Gama L, Li M, Bartizal CM, Queen SE, Varrone JJ, Brice AK, Graham, DR , Tarwater PM, Mankowski JL, Zink, MC, and CLEMENTS, JE. Coordinated Regulation of SIV Replication and Immune Responses in the CNS. PLoS One. 4(12):e8129, 2009.
PubMed Ref
 

Shruthi Ravimohan, S, Gama, l, Barber, SA, CLEMENTS, JE. Regulation of SIVmac239 Basal LTR Activity and Viral Replication in Macrophages: Functional Roles of Two C/EBP sites in Activation and IFN-Mediated Suppression. J Biol Chem. 285(4):2258-73, 2009.
PubMed Ref

Wright EK, Page, SH, Barber SA, CLEMENTS JE. Prep1/Pbx2 Complexes Regulate CCL2 Expression Through the –2578 Guanine Polymorphism. Nature, Genes and Immunity, 9(5):419-30, 2008.
PubMed Ref

Dudaronek , JM, Barber, SA, CLEMENTS, JE. CUGBP1 is Required for IFN-Mediated Induction of Dominant-Negative CEBP and Suppression of SIV Replication in Macrophages. J. Immunology; 179(11):7262-9, 2007.
PubMed Ref

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