Klaus Strebel, Ph.D.

Senior Investigator

Viral Biochemistry Section

NIAID/DIR

Building 4, Room 312
4 Memorial Drive
Bethesda, MD 20892

301-496-3132

kstrebel@niaid.nih.gov

Research Topics

Primate immunodeficiency viruses, including HIV-1, are characterized by the presence of accessory genes such as vifvprvpx,vpu, and nef. Current knowledge indicates that none of these proteins has enzymatic activity. Instead, they interact with cellular ligands either to act as adapter molecules to redirect the normal function of host factors for virus-specific purposes or to inhibit a normal host function by mediating degradation or causing intracellular mislocalization/sequestration of the factors involved.

The primary objective of the Viral Biochemistry Section is to investigate the biological and biochemical functions of HIV accessory proteins, in particular Vif, Vpu, and Vpx, and to define their role in virus replication. This includes both the detailed biological and biochemical characterization of the individual viral proteins as well as the investigation of their engagement with distinct host factors. Understanding the molecular mechanisms of viral proteins will benefit our general understanding of the HIV replication process and may reveal new targets for antiviral therapy. In addition, the investigation of virus-host interactions will give us new insights into general cellular processes involved in protein trafficking, degradation, post-translational modification, and so forth.

Our early study on Vpu-induced degradation of the HIV receptor CD4 presented the first example in the HIV literature of the engagement of the host proteasome machinery in the control of cellular proteins by HIV accessory proteins (Willey et al., JVI 66:7193 [1992]). Since then, similar strategies, although mechanistically distinct, were identified for the control of BST-2 by Vpu, APOBEC3G by Vif, or SAMHD1 by the Vpx protein. Thus, the control of host mechanisms through proteolytic degradation of cellular targets is a common theme in HIV biology and remains an intense focus of our research. Modulating the intracellular localization of host factors is another popular strategy employed by viruses to control their function and/or to subvert it to benefit the virus. Examples under investigation in the lab are the down-modulation of BST-2 from the cell surface with subsequent degradation through the lysosomal pathway or the sequestration of APOBEC3G away from the site of virus assembly.

Biography

Dr. Strebel received his Ph.D. in microbiology in 1985 from the University of Heidelberg, Germany. After postdoctoral research in Germany on foot-and-mouth disease protein processing and maturation, he joined the Laboratory of Molecular Microbiology (LMM) in 1986 as a postdoctoral fellow to work on molecular mechanisms of HIV-1 replication. He was awarded tenure in 1998 and, since 2000, has been chief of the Viral Biochemistry Section within LMM.

Selected Publications


This page was last updated on February 15th, 2017