Open AccessReplication of Beta- and Gammaretroviruses Is Restricted in I/LnJ Mice via the Same Genetic Mechanism
Author(s) -
Laure K. Case,
Lydia M. Petell,
Leonid Yurkovetskiy,
Alexandra E. Purdy,
Katherine J. Savage,
Tatyana V. Golovkina
Publication year - 2008
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01991-07
Subject(s) - biology , virology , virus , murine leukemia virus , mouse mammary tumor virus , neutralizing antibody , immune system , retrovirus , viral replication , gammaretrovirus , immunology
Mice of the I/LnJ inbred strain are unique in their ability to mount a robust and sustained humoral immune response capable of neutralizing infection with a betaretrovirus, mouse mammary tumor virus (MMTV). Virus-neutralizing antibodies (Abs) coat MMTV virions secreted by infected cells, preventing virus spread and hence the formation of mammary tumors. To investigate whether I/LnJ mice resist infection with other retroviruses besides MMTV, the animals were infected with murine leukemia virus (MuLV), a gammaretrovirus. MuLV-infected I/LnJ mice produced virus-neutralizing Abs that block virus transmission and virally induced disease. Generation of virus-neutralizing Abs required gamma interferon but was independent of interleukin-12. This unique mechanism of retrovirus resistance is governed by a single recessive gene,v irusi nfectivityc ontroller1 (vic1 ), mapped to chromosome 17. In addition to controlling the antivirus humoral immune response,vic1 is also required for an antiviral cytotoxic response. Both types of responses were maintained in mice of the susceptible genetic background but congenic for the I/LnJvic1 locus. Although thevic1 -mediated resistance to MuLV resembles the mechanism of retroviral recovery controlled by ther esistance toF riendv irus3 (rfv3 ) gene, therfv3 gene has been mapped to chromosome 15 and confers resistance to MuLV but not to MMTV. Thus, we have identified a unique virus resistance mechanism that controls immunity against two distinct retroviruses.