HIV-related Research OverviewSteve Zeichner, MD, PhD

Sr. Investigator, Division of Cancer and ImmunologyChildrens Research Institute, Childrens National Medical CenterAssoc. Prof., Dept of Pediatrics & Microbiology, GWUMC

SZeichne@cnmc.org202-884-6131

Research AreasHIV basic virologyVirus-host cell interactionsEffect of viral genes on the host cellCellular genes involved in the maintenance and control of HIV latencyKSHV basic virologyControl of KSHV gene expressionClinical studies on pediatric HIV disease

Effect of Vpr on Host Cell Gene Expression

Models for Vpr-mediated Cell Cycle Arrest

Hierarchical clustering of differentially expressed host cell genes before and after induction of lytic infection in ACH-2 cells.

ConclusionsLatently infected cell lines show differences in cell gene expression compared to parental cells before lytic replication.Agents targeting products of genes differentially expressed in latently infected cells can eject HIV from latency.Such studies may suggest new ways of manipulating HIV latency, which might find clinical utility in studies aimed atassessing efficacy of reservoir reduction.

Effect of the Viral DNA ReplicationInhibitor CidofovirOn the Viral GeneExpression PatternColor: - CDVBlack: + CDV

Ras and Ras-related genes upregulated in lytically replicating ACH-2. Abl-kinase regulates Ras.Ras and abl-kinase synergistically activate NF-kB.NF-kB is a key positive regulator of HIV gene expression.Can an abl-kinase inhibitor inhibit HIV replication?

Reeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg MB, Veach D, Bornmann W, Sherman M, Kalman D.

Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases.Nat Med. 2005 Jul;11(7):731-9. Epub 2005 Jun 26