Rajesh Ramakrishnan

Summary

Affiliation: Baylor College of Medicine
Location: Houston, USA
Summary:
Elucidating molecular mechanisms of mother-to-child transmission of HIV-1. Phylogenetic analysis of HIV-1 genes from infected PBMCs of mothers and their infants reveal a degree of conservation of open reading frames and domains. The virus replicates at a much higher level in neonatal PBMCs than adult PBMCs and is regulated at the level of viral gene expression and site of integration.
Analysis of essential host factors for HIV-1 replication shows that Cdk9 ( kinase subunit of P-TEFb recruited by HIV-1 Tat protein for viral gene expression) is regulated in resting CD4 T-cells at the level of phosphorylation. The phosphorylation of Thr186 in the T-loop of Cdk9 is critical for Cdk9 function. Cdk9 T-loop phosphorylation is very low in resting cells and is induced rapidly upon T-cell activation without need for de novo protein synthesis. Cdk9 T-loop phosphorylation is regulated by Calcium signaling.
Publications:
1. J Cell Physiol. 2011 Mar 29. doi: 10.1002/jcp.22760. [Epub ahead of print]

Cdk9 T-loop phosphorylation is regulated by the calcium signaling pathway.

Ramakrishnan R, Rice AP.

Department of Molecular Virology and Microbiology, Baylor College of Medicine,
One Baylor Plaza, Houston, TX 77030, USA.
PMID: [PubMed - as supplied by publisher]

2. J Leukoc Biol. 2009 Dec;86(6):1345-50. Epub 2009 Sep 10.

Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T
lymphocytes.

Ramakrishnan R, Dow EC, Rice AP.

Department of Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, Texas 77030, USA.

PMCID: PMC2780919
PMID: [PubMed - indexed for MEDLINE]

3. Virology. 2009 Mar 1;385(1):28-38. Epub 2008 Dec 18.

Differential HIV-1 integration targets more actively transcribed host genes in
neonatal than adult blood mononuclear cells.

Wellensiek BP, Ramakrishnan R, Sundaravaradan V, Mehta R, Harris DT, Ahmad N.

Department of Immunobiology, University of Arizona, Tucson, 85724, USA.

PMID: [PubMed - indexed for MEDLINE]


4. J Biol Chem. 2008 Nov 28;283(48):33578-84. Epub 2008 Oct 1.

Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop.

Wang Y, Dow EC, Liang YY, Ramakrishnan R, Liu H, Sung TL, Lin X, Rice AP.

Department of Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, Texas 77030, USA.

PMCID: PMC2586277
PMID: [PubMed - indexed for MEDLINE]


5. PLoS One. 2008 Sep 5;3(9):e3146.

Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear
enriched in HIV-1 co-factors.

Yu W, Ramakrishnan R, Wang Y, Chiang K, Sung TL, Rice AP.

Department of Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, Texas, United States of America.

PMCID: PMC2519787
PMID: [PubMed - indexed for MEDLINE]


6. AIDS Res Hum Retroviruses. 2008 Mar;24(3):437-45.

Genetic characterization of HIV type 1 long terminal repeat following vertical
transmission.

Mehta R, Ramakrishnan R, Doktor K, Sundaravaradan V, Ahmad N.

Department of Immunobiology, College of Medicine, The University of Arizona
Health Sciences Center, Tucson, Arizona 85724, USA.

PMID: [PubMed - indexed for MEDLINE]


7. Virol J. 2007 Nov 24;4:126.

Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor
utilization and replication efficiency in primary T-lymphocytes and
monocyte-derived macrophages.

Sundaravaradan V, Das SR, Ramakrishnan R, Sehgal S, Gopalan S, Ahmad N, Jameel S.

Department of Immunobiology, College of Medicine, University of Arizona, Tucson,
AZ 85724, USA. vsvaradan@yahoo.com

PMCID: PMC2216014
PMID: [PubMed - indexed for MEDLINE]


8. Virology. 2007 Mar 1;359(1):201-11. Epub 2006 Oct 11.

Derivation of primary sequences and secondary structures of rev responsive
element from HIV-1 infected mothers and infants following vertical transmission.

Ramakrishnan R, Ahmad N.

Department of Immunobiology, College of Medicine, The University of Arizona
Health Sciences Center, Tucson, AZ 85724, USA.

PMID: [PubMed - indexed for MEDLINE]


9. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11701-6. Epub 2006 Jul 25.

Differential HIV-1 replication in neonatal and adult blood mononuclear cells is
influenced at the level of HIV-1 gene expression.

Sundaravaradan V, Saxena SK, Ramakrishnan R, Yedavalli VR, Harris DT, Ahmad N.

Department of Microbiology and Immunology, College of Medicine, University of
Arizona, Tucson, AZ 85724, USA.


PMCID: PMC1544233
PMID: [PubMed - indexed for MEDLINE]


10. Retrovirology. 2006 Jul 4;3:42.

Characterization of HIV-1 envelope gp41 genetic diversity and functional domains
following perinatal transmission.

Ramakrishnan R, Mehta R, Sundaravaradan V, Davis T, Ahmad N.

Department of Microbiology and Immunology, College of Medicine, The University of
Arizona Health Sciences Center, Tucson, Arizona 85724, USA. ramakris@bcm.tmc.edu


PMCID: PMC1526753
PMID: [PubMed - indexed for MEDLINE]


11. Retrovirology. 2006 Apr 6;3:21.

Molecular characterization of the HIV-1 gag nucleocapsid gene associated with
vertical transmission.

Wellensiek BP, Sundaravaradan V, Ramakrishnan R, Ahmad N.

Department of Microbiology and Immunology, College of Medicine, The University of
Arizona Health Sciences Center, Tucson, Arizona, USA. bwellen1@u.arizona.edu


PMCID: PMC1459197
PMID: [PubMed - indexed for MEDLINE]


12. AIDS Res Hum Retroviruses. 2005 Dec;21(12):1035-45.

Evaluations of HIV type 1 rev gene diversity and functional domains following
perinatal transmission.

Ramakrishnan R, Hussain M, Holzer A, Mehta R, Sundaravaradan V, Ahmad N.

Department of Microbiology and Immunology, College of Medicine, The University of
Arizona Health Sciences Center, Tucson, Arizona 85724, USA.


PMID: [PubMed - indexed for MEDLINE]


13. J Biomed Sci. 2003 Jul-Aug;10(4):436-50.

Evaluation of genetic diversity of human immunodeficiency virus type 1 NEF gene
associated with vertical transmission.

Hahn T, Ramakrishnan R, Ahmad N.

Department of Microbiology and Immunology, College of Medicine, The University of
Arizona Health Sciences Center, Tucson, AZ 85724, USA.


PMID: [PubMed - indexed for MEDLINE]

Publications

  1. ncbi Evaluation of genetic diversity of human immunodeficiency virus type 1 NEF gene associated with vertical transmission
    Tobias Hahn
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    J Biomed Sci 10:436-50. 2003
  2. pmc Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Leukoc Biol 86:1345-50. 2009
  3. doi Differential HIV-1 integration targets more actively transcribed host genes in neonatal than adult blood mononuclear cells
    Brian P Wellensiek
    Department of Immunobiology, University of Arizona, Tucson, 85724, USA
    Virology 385:28-38. 2009
  4. pmc Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop
    Yan Wang
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 283:33578-84. 2008
  5. pmc Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors
    Wendong Yu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 3:e3146. 2008
  6. doi Genetic characterization of HIV type 1 long terminal repeat following vertical transmission
    Roshni Mehta
    Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    AIDS Res Hum Retroviruses 24:437-45. 2008
  7. pmc Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages
    Vasudha Sundaravaradan
    Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
    Virol J 4:126. 2007
  8. ncbi Derivation of primary sequences and secondary structures of rev responsive element from HIV-1 infected mothers and infants following vertical transmission
    Rajesh Ramakrishnan
    Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    Virology 359:201-11. 2007
  9. pmc Differential HIV-1 replication in neonatal and adult blood mononuclear cells is influenced at the level of HIV-1 gene expression
    Vasudha Sundaravaradan
    Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
    Proc Natl Acad Sci U S A 103:11701-6. 2006
  10. pmc Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission
    Rajesh Ramakrishnan
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    Retrovirology 3:42. 2006

Detail Information

Publications15

  1. ncbi Evaluation of genetic diversity of human immunodeficiency virus type 1 NEF gene associated with vertical transmission
    Tobias Hahn
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    J Biomed Sci 10:436-50. 2003
    ....
  2. pmc Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Leukoc Biol 86:1345-50. 2009
    ....
  3. doi Differential HIV-1 integration targets more actively transcribed host genes in neonatal than adult blood mononuclear cells
    Brian P Wellensiek
    Department of Immunobiology, University of Arizona, Tucson, 85724, USA
    Virology 385:28-38. 2009
    ....
  4. pmc Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop
    Yan Wang
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 283:33578-84. 2008
    ..PPM1B only efficiently dephosphorylated Cdk9 Thr-186 in vitro when 7SK RNA was depleted from P-TEFb. Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function...
  5. pmc Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors
    Wendong Yu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 3:e3146. 2008
    ..The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors...
  6. doi Genetic characterization of HIV type 1 long terminal repeat following vertical transmission
    Roshni Mehta
    Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    AIDS Res Hum Retroviruses 24:437-45. 2008
    ....
  7. pmc Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages
    Vasudha Sundaravaradan
    Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
    Virol J 4:126. 2007
    ..Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2), coreceptor cell lines (U373-MAGI-CCR5/CXCR4), primary blood T-lymphocytes (PBL) and monocyte-derived macrophages (MDM)...
  8. ncbi Derivation of primary sequences and secondary structures of rev responsive element from HIV-1 infected mothers and infants following vertical transmission
    Rajesh Ramakrishnan
    Department of Immunobiology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    Virology 359:201-11. 2007
    ....
  9. pmc Differential HIV-1 replication in neonatal and adult blood mononuclear cells is influenced at the level of HIV-1 gene expression
    Vasudha Sundaravaradan
    Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
    Proc Natl Acad Sci U S A 103:11701-6. 2006
    ....
  10. pmc Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission
    Rajesh Ramakrishnan
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    Retrovirology 3:42. 2006
    ..We, therefore, characterized the molecular properties of gp41, including genetic diversity, functional motifs, and evolutionary dynamics from five mother-infant pairs following perinatal transmission...
  11. pmc Molecular characterization of the HIV-1 gag nucleocapsid gene associated with vertical transmission
    Brian P Wellensiek
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona, USA
    Retrovirology 3:21. 2006
    ....
  12. ncbi Evaluations of HIV type 1 rev gene diversity and functional domains following perinatal transmission
    Rajesh Ramakrishnan
    Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA
    AIDS Res Hum Retroviruses 21:1035-45. 2005
    ..The conservation of functional domains of rev and a low degree of heterogeneity following vertical transmission are consistent with an indispensable role of rev in the HIV-1 life cycle...
  13. pmc Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4(+) T cells and inhibits HIV-1 gene expression
    Sona Budhiraja
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    Retrovirology 9:52. 2012
    ..We investigated the role of phosphatase PPM1A in regulating CDK9 T-loop phosphorylation and its effect on HIV-1 proviral transcription...
  14. pmc Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
    BMC Res Notes 4:260. 2011
    ..abstract:..
  15. pmc Identification of novel CDK9 and Cyclin T1-associated protein complexes (CCAPs) whose siRNA depletion enhances HIV-1 Tat function
    Rajesh Ramakrishnan
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
    Retrovirology 9:90. 2012
    ..Nine CCAPs are novel, while three were previously identified as Core P-TEFb, the 7SK snRNP, and the Super-Elongation Complex. We have investigated the role of five newly identified CCAPs in Tat function and viral gene expression...