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Title: Avian sarcoma and leukosis virus-receptor interactions: From classical genetics to novel insights into virus-cell membrane fusion

Abstract

For over 40 years, avian sarcoma and leukosis virus (ASLV)-receptor interactions have been employed as a useful model system to study the mechanism of retroviral entry into cells. Pioneering studies on this system focused upon the genetic basis of the differential susceptibilities of different lines of chickens to infection by distinct subgroups of ASLV. These studies led to the definition of three distinct autosomal recessive genes that were predicted to encode cellular receptors for different viral subgroups. They also led to the concept of viral interference, i.e. the mechanism by which infection by one virus can render cells resistant to reinfection by other viruses that use the same cellular receptor. Here, we review the contributions that analyses of the ASLV-receptor system have made in unraveling the mechanisms of retroviral entry into cells and focus on key findings such as identification and characterization of the ASLV receptor genes and the subsequent elucidation of an unprecedented mechanism of virus-cell fusion. Since many of the initial findings on this system were published in the early volumes of Virology, this subject is especially well suited to this special anniversary issue of the journal.

Authors:
 [1];  [1];  [2]
  1. Infectious Disease Laboratory, Salk Institute, La Jolla, San Diego, CA 92037-1099 (United States)
  2. Infectious Disease Laboratory, Salk Institute, La Jolla, San Diego, CA 92037-1099 (United States). E-mail: jyoung@salk.edu
Publication Date:
OSTI Identifier:
20779446
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 344; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2005.09.021; PII: S0042-6822(05)00590-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL MEMBRANES; CHICKENS; GENETICS; RECEPTORS; SARCOMAS; VIRUSES

Citation Formats

Barnard, R.J.O., Elleder, D., and Young, J.A.T. Avian sarcoma and leukosis virus-receptor interactions: From classical genetics to novel insights into virus-cell membrane fusion. United States: N. p., 2006. Web. doi:10.1016/J.VIROL.2005.0.
Barnard, R.J.O., Elleder, D., & Young, J.A.T. Avian sarcoma and leukosis virus-receptor interactions: From classical genetics to novel insights into virus-cell membrane fusion. United States. doi:10.1016/J.VIROL.2005.0.
Barnard, R.J.O., Elleder, D., and Young, J.A.T. Thu . "Avian sarcoma and leukosis virus-receptor interactions: From classical genetics to novel insights into virus-cell membrane fusion". United States. doi:10.1016/J.VIROL.2005.0.
@article{osti_20779446,
title = {Avian sarcoma and leukosis virus-receptor interactions: From classical genetics to novel insights into virus-cell membrane fusion},
author = {Barnard, R.J.O. and Elleder, D. and Young, J.A.T.},
abstractNote = {For over 40 years, avian sarcoma and leukosis virus (ASLV)-receptor interactions have been employed as a useful model system to study the mechanism of retroviral entry into cells. Pioneering studies on this system focused upon the genetic basis of the differential susceptibilities of different lines of chickens to infection by distinct subgroups of ASLV. These studies led to the definition of three distinct autosomal recessive genes that were predicted to encode cellular receptors for different viral subgroups. They also led to the concept of viral interference, i.e. the mechanism by which infection by one virus can render cells resistant to reinfection by other viruses that use the same cellular receptor. Here, we review the contributions that analyses of the ASLV-receptor system have made in unraveling the mechanisms of retroviral entry into cells and focus on key findings such as identification and characterization of the ASLV receptor genes and the subsequent elucidation of an unprecedented mechanism of virus-cell fusion. Since many of the initial findings on this system were published in the early volumes of Virology, this subject is especially well suited to this special anniversary issue of the journal.},
doi = {10.1016/J.VIROL.2005.0},
journal = {Virology},
number = 1,
volume = 344,
place = {United States},
year = {Thu Jan 05 00:00:00 EST 2006},
month = {Thu Jan 05 00:00:00 EST 2006}
}
  • The authors have constructed an avian leukosis virus derivative with a 5{prime} deletion extending from within the tRNA primer binding site to a SacI site in the leader region. The aim was to remove cis-acting replicative and/or encapsidation sequences and to use this derivative, RAV-1{Psi}{sup {minus}}, to develop vector-packaging cell lines. They show that RAV-1{Psi}{sup {minus}} can be stably expressed in the quail cell line QT6 and chicken embryo fibroblasts and that it is completely replication deficient in both cell types. Moreover, they have demonstrated that QT6-derived lines expressing RAV-1{Psi}{sup {minus}} can efficiently package four structurally different replication-defective v-src expressionmore » vectors into infectious virus, with very low or undetectable helper virus release. These RAV-{Psi}{sup {minus}}-expressing cell lines comprise the first prototype avian sarcoma and leukosis virus-based vector-packaging system. The construction of our vectors has also shown us that a sequence present within gag, thought to facilitate virus packaging, is not necessary for efficient vector expression and high virus production. They show that quantitation and characterization of replication-defective viruses can be achieved with a sensitive immunocytochemical procedure, presenting an alternative to internal selectable vector markers.« less
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  • Early embryonic avian tissue is resistant to transformation by Rous sarcoma virus. To determine the nature of this resistance, the authors examined the expression and properties of the Rous sarcoma virus transforming protein pp60{sup v-src}, in infected embryonic chicken limbs in ovo. Lysates from Rous sarcoma virus-infected limbs contained the viral structural protein p19{sup gag}, as detected by immunoblot analysis and showed pp60{sup v-src} kinase activity in vitro. Immunoblot analysis of lysates with anti-phosphotyrosine antibodies revealed a number of phosphotyrosine-containing proteins present in lysates of Rous sarcoma virus-infected embryos but not in lysates of control, uninfected embryos. These studies demonstratemore » that pp60{sup v-src} is co-expressed with viral structural determinants in infected embryonic avian tissue. The localization pattern of the major src gene substrate p36 (calpactin I) was compared with that of p19{sup gag} by double-label immunofluorescence and found to be generally nonoverlapping. These observations are consistent with the concept that the induction of tumors in ovo requires complementation between viral determinants and host factors. These host factors, which may be critical substrates of pp60{sup src}, are subject to developmental regulation in the avian embryo.« less