Sequence heterogeneity of murine acquired immunodeficiency syndrome virus: the role of endogenous virus

Abstract

A defective murine leukemia virus is the causative agent of murine acquired immunodeficiency syndrome (MAIDS). We have cloned cDNAs from both virus infected and non-infected cells using the PCR methods with primers corresponding to the franking sequence of the unique p12 gag gene. Sequence analysis of these cDNA clones revealed: (i) the presence of endogenous virus related to MAIDS virus in C57BL/6 mice, (ii) B cell lineage specific expression of endogenous virus and (iii) extensive heterogeneity of MAIDS virus recovered from virus infected cells due to the recombination of the related viruses (defective pathogenic virus, ecotropic virus and endogenous virus). These findings suggest that the creation of virus variants in infected cells may play an important role in virus pathogenesis and escape from immune attack during the development of MAIDS.

Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome: Involvement of Fas‐Fas ligand interaction

“…Recently, we have shown the extensive heterogeneity of MAIDS viruses recovered from infected cells [29]. Although we do not know at present the exact nature of the MAIDS virus-associated superantigens, it is possible that, in MAIDS virus infected mice, multiple superantigens encoded by heterogeneous viruses interact with different sets of Tcells simultaneously.…”

Superantigens related to B cell hyperplasia

“…Under normal conditions the low expression of the vSAgs encoded by mtv-8 and mtv-9 in resting B cells from C57BL mice, particularly in the absence of MHC class II I-E, which is thought to promote the presentation of these vSAgs, is apparently insufficient to cause stimulation or deletion of the V/35-and V/311-bearing T cells [132]. Such activated B cells, which are clearly needed for the development of MAIDS [19,64] cause a skewed T cell repertoire in the periphery, which may partially be due to a vSAg function of Pr60gag, and partially also be the result of enhanced presentation of the endogenous mtv-8-LTRand mtv-9-LTR-encoded vSAgs [45,70,75,129]. Such activated B cells, which are clearly needed for the development of MAIDS [19,64] cause a skewed T cell repertoire in the periphery, which may partially be due to a vSAg function of Pr60gag, and partially also be the result of enhanced presentation of the endogenous mtv-8-LTRand mtv-9-LTR-encoded vSAgs [45,70,75,129].…”

Possible origin of murine AIDS (MAIDS) virus: conversion of an endogenous retroviral p12gag sequence to a MAIDS-inducing sequence by frameshift mutations

“…Normal C57BL/6 mice express a transcript which hybridizes with the MAIDS virus p12 gag sequence (5,6), and previously we cloned and sequenced this transcript (Edv) (15). There are some other lines of evidence indicating that normal mice contain the MAIDS virus-related sequence (3,7,10). Since the MAIDS virus was originally isolated from radiation-induced leukemic C57BL/6 mice (18), the Edv transcript expressed in C57BL/6 mice might represent the origin of the MAIDS virus.…”