Schumann G, Boeke JD; Keystone Symposia on Molecular and Cellular Biology: 1998 HIV Pathogenesis and Treatment.

Keyst Symp Mol Cell Biol Keyst Symp Mol Cell Biol. 1998 Mar 13-19; 53 (abstract no. 2025).

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD.

A novel strategy for neutralizing retroviral infectivity is to induce the incorporation of lethal fusion proteins into the virion during the normal viral assembly process. This "intracellular immunization" strategy is called "capsid-targeted viral inactivation" (CTVI), and was demonstrated to be highly efficient against M-MuLV and HIV-1 in cultured cells. The stable reduction of infectious virus output in cell culture was 20-100 fold. We have fused Staphylococcal nuclease (SN) to the C-terminal end of M-MuLV Gag and generated transgenic mouse lines expressing M-MuLV Gag-SN fusion proteins in order to test this antiviral strategy in an animal model. We crossed mice transgenic for an integrated; active leukemogenic M-MuLV provirus (Mov13 heterozygote mice) with our lines expressing the antiviral fusion protein. Infectious titers in sera of the resulting Mov13 progeny expressing antiviral Gag-SN fusion proteins were reduced 2-10 fold relative to siblings that do not express Gag-SN. Preliminary data show that Gag-SN expression has a positive effect on the lifespan and an inhibitory effect on the enlargement of the spleen in Mov13 mice. These studies on transgenic mice provide the first in vivo model system for the effectiveness of CTVI as an antiviral strategy.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Antiviral Agents
• Capsid
• Capsid Proteins
• Gene Products, gag
• Genes, gag
• HIV-1
• Mice
• Mice, Transgenic
• Micrococcal Nuclease
• Recombinant Fusion Proteins
• Retroviridae
• Virion
• Virus Inactivation
• genetics
• virology

Other ID:

• 98930314

UI: 102236742

From Meeting Abstracts