Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus

Kenneth S. Chan, Paulo H. Verardi, Fatema A. Legrand, Tilahun Yilma

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)8734-8739
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 14 2005


  • Attenuation
  • Atypical plaque formation
  • Lentiviruses
  • Poxviruses
  • Virulence

ASJC Scopus subject areas

  • Genetics
  • General


Dive into the research topics of 'Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus'. Together they form a unique fingerprint.

Cite this