Interferons (IFNs) have an unusual mechanism of action against some membrane-associated viruses. IFN-treated cells produce defective virus particles that have decreased infectivity because they are deficient in a membrane-associated glycoprotein. This is the principal antiviral activity of IFNs against retroviruses, but it is also an important mechanism for inhibiting the replication of vesicular stomatitis virus (VSV) in some cells such as IFN-treated LB cells which produce VSV particles of low infectivity that are deficient in VSV-G glycoprotein. In the IFN-treated cells G does not efficiently localize in the plasma membrane from which site it is ordinarily incorporated into budding VSV particles. Recent findings indicate that in IFN- treated cells the G protein of VSV is inefficiently transported to the plasma membrane from a cytoplasmic structure. Preliminary biochemical and morphological data suggest that this structure is the trans compartment of the Golgi complex (GC).
The aims of this proposal are to analyze this localization in a clone of LB cells in which a large majority of the cells clearly manifest the cytoplasmic localization of G in IFN-treated cells. Experiments in IFN-treated cells will be carried out to study the morphological and biochemical localization of G. We also plan to analyze the transport of G protein within the GC. Other experiments will be focused on what biochemical effects of IFN might be involved in the inhibition of G transport such as changes in the pH of acid vesicles, in the fatty-acid composition of the cell, or in association of G with membranes. These studies may be useful in enlarging our understanding of how proteins are targeted by processing.
| Maheshwari, R K; Sidhu, G S; Bhartiya, D et al. (1991) Primary amines enhance the antiviral activity of interferon against a membrane virus: role of intracellular pH. J Gen Virol 72 ( Pt 9):2143-52 |
| Gendelman, H E; Baca, L; Turpin, J A et al. (1990) Restriction of HIV replication in infected T cells and monocytes by interferon-alpha. AIDS Res Hum Retroviruses 6:1045-9 |
| Black, R J (1989) Cytokines and oncogenes. J Exp Pathol 4:109-21 |
| Black, R J; Friedman, R M (1989) Cytokines and oncogene activity. Cancer Surv 8:725-39 |
| Rimoldi, D; Samid, D; Flessate, D M et al. (1988) Transcriptional inhibition of Ha-ras in interferon-induced revertants of ras-transformed mouse cells. Cancer Res 48:5157-62 |
| Singh, V K; Maheshwari, R K; Damewood 4th, G P et al. (1988) Interferon alters intracellular transport of vesicular stomatitis virus glycoprotein. J Biol Regul Homeost Agents 2:53-62 |
| Samid, D; Flessate, D M; Friedman, R M (1987) Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine. Mol Cell Biol 7:2196-200 |
| Panigrahi, P; Mohanty, S B; Maheshwari, R K et al. (1987) Structural proteins of bovine parainfluenza-3 virus. Vet Microbiol 13:205-10 |
| Maheshwari, R K; Friedman, R M (1985) Interferon induced inhibition of enveloped viruses. Prog Clin Biol Res 202:297-305 |
| Singh, V K; Maheshwari, R K; Krishna, G et al. (1985) Effects of interferon on calcium. Prog Clin Biol Res 202:351-6 |
Showing the most recent 10 out of 12 publications
