Retrovirology: Research and Treatment

Institute for Molecular Virology, Saint Louis University Health Sciences Center, Saint Louis, MO 63104. U.S.A.

Abstract

Human immunodeficiency virus type-1 integrase (IN) is a new and novel target for inhibitors. Strand transfer inhibitors effectively prevent concerted integration of viral DNA by IN into the host chromosomes. Raltegravir is the first approved strand transfer inhibitor for the treatment of HIV-1/AIDS. We propose a mechanistic hypothesis as to “when and where” these inhibitors are active in virus-infected cells. Using native agarose gel electrophoresis, we identified a transient synaptic complex (SC) wherein IN non-covalently juxtaposes two viral DNA ends. SC possesses many properties associated with the cytoplasmic preintegration complex (PIC) in infected cells, including concerted integration. Our results show that the strand transfer inhibitors effectively “trap” or inactivate the SC preventing concerted integration. It follows that the IN-viral DNA complex is “trapped” by the inhibitors via a transient intermediate within the cytosolic PIC before entry into the nucleus.

Interview

Read an interview with Dr Pandey here.