Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus
| Autor: | Fatema A. Legrand, Kenneth S. Chan, Paulo H. Verardi, Tilahun Yilma |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Viral Plaque Assay
viruses Immunoblotting Mice Nude Virulence Vaccinia virus Biology Virus Replication medicine.disease_cause Virus Mice chemistry.chemical_compound medicine Animals Viral Regulatory and Accessory Proteins RNA Messenger Crosses Genetic Immunodeficiency DNA Primers Multidisciplinary virus diseases Biological Sciences Simian immunodeficiency virus medicine.disease Virology Actins Microscopy Fluorescence chemistry Viral replication Thymidine kinase Simian Immunodeficiency Virus Vaccinia |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:8734-8739 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0503542102 |
| Popis: | The nef gene of human and simian immunodeficiency viruses (HIV and SIV) is important for pathogenicity and maintenance of high virus loads. We previously reported that recombinant vaccinia viruses (rVVs) expressing nef from attenuated SIVmac1A11 (vNef1A11) produced typical plaques on thymidine kinase-deficient 143B cells, whereas rVVs expressing nef derived from the pathogenic SIVmac239 (vNef157) formed plaques with altered morphology. Here, we show that vNef157 is attenuated in normal and nude mice, whereas the pathogenicity of vNef1A11 is similar to that of a control virus. Thus, Nef157 is an attenuating factor in the vaccinia virus (VV) system, contrasting sharply with its function in lentiviruses. We also show that Nef157 inhibits VV cell-to-cell spread, causing formation of atypical plaques regardless of thymidine kinase deficiency, neoplasticity, and species of the infected cell line. We hypothesized that Nef157 interferes with VV spread by association with actin, but no direct colocalization of Nef and the cytoskeletal actin network was detected. Instead, higher levels of Nef157 protein were observed, although mRNAs for both nef genes were produced at comparable levels. Thus, the mechanism behind such Nef157 protein accumulation and Nef157-mediated VV attenuation could be related to the process that causes an opposite effect in its native SIV system, making SIVmac239 more pathogenic than SIVmac1A11. |
| Databáze: | OpenAIRE |
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