1. HIV-related Research Overview
Steve Zeichner, MD, PhD
Sr. Investigator, Division of Cancer and Immunology
Children’s Research Institute,
Children’s National Medical Center
Assoc. Prof., Dept of Pediatrics & Microbiology, GWUMC

2. Research Areas HIV basic virology KSHV basic virology
Virus-host cell interactions
Effect of viral genes on the host cell
Cellular genes involved in the maintenance and control of HIV latency
KSHV basic virology
Control of KSHV gene expression
Clinical studies on pediatric HIV disease

3. Effect of Vpr on Host Cell Gene Expression

4. Models for Vpr-mediated Cell Cycle Arrest

5. Hierarchical clustering of differentially expressed host cell genes before and after induction of lytic infection in ACH-2 cells.
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 Jul;11(7): Epub 2005 Jun 26

6. Conclusions Latently 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 at
assessing efficacy of reservoir reduction.

9. Effect of the
Viral DNA Replication
Inhibitor Cidofovir
On the Viral Gene
Expression Pattern
Color: - CDV
Black: + CDV