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 journalArticle

6 Citations (Scopus)

Abstract

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
Volume102
Issue number24
DOIs
StatePublished - Jun 14 2005

Fingerprint

Simian Immunodeficiency Virus
Vaccinia virus
nef Genes
Thymidine Kinase
Virulence
Actins
HIV
Viruses
Lentivirus
Nude Mice
Proteins
Cell Line
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus. / Chan, Kenneth S.; Verardi, Paulo H.; Legrand, Fatema A.; Yilma, Tilahun.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 24, 14.06.2005, p. 8734-8739.

Research output: Contribution to journalArticle

@article{02bbb50fd1424fb7a9291597d829efed,
title = "Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus",
abstract = "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.",
keywords = "Attenuation, Atypical plaque formation, Lentiviruses, Poxviruses, Virulence",
author = "Chan, {Kenneth S.} and Verardi, {Paulo H.} and Legrand, {Fatema A.} and Tilahun Yilma",
year = "2005",
month = "6",
day = "14",
doi = "10.1073/pnas.0503542102",
language = "English (US)",
volume = "102",
pages = "8734--8739",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

TY - JOUR

T1 - Nef from pathogenic simian immunodeficiency virus is a negative factor for vaccinia virus

AU - Chan, Kenneth S.

AU - Verardi, Paulo H.

AU - Legrand, Fatema A.

AU - Yilma, Tilahun

PY - 2005/6/14

Y1 - 2005/6/14

N2 - 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.

AB - 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.

KW - Attenuation

KW - Atypical plaque formation

KW - Lentiviruses

KW - Poxviruses

KW - Virulence

UR - http://www.scopus.com/inward/record.url?scp=20844436465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20844436465&partnerID=8YFLogxK

U2 - 10.1073/pnas.0503542102

DO - 10.1073/pnas.0503542102

M3 - Article

C2 - 15930136

AN - SCOPUS:20844436465

VL - 102

SP - 8734

EP - 8739

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 24

ER -