Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus.
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.
Chan
Kenneth S
KS
International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Verardi
Paulo H
PH
Legrand
Fatema A
FA
Yilma
Tilahun D
TD
D000199:Actins / Q000378:metabolism; D000818:Animals; D003433:Crosses, Genetic; D017931:DNA Primers; D015151:Immunoblotting; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014616:Vaccinia virus / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity*; D010948:Viral Plaque Assay; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication / Q000502:physiology*
D000199:Actins; D017931:DNA Primers; C429284:NEF protein, SIV; D012333:RNA, Messenger; D054334:Viral Regulatory and Accessory Proteins