The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage

Abstract

Murine AIDS (MAIDS) is caused by a defective retrovirus which encodes a gag fusion protein (Pr60gag). We previously reported that this virus induced an oligoclonal proliferation of infected cells and suggested that this cell expansion was an important event in the pathogenesis of MAIDS. To identify these target cells, we constructed novel defective viruses whose genomes could be detected with specific probes. Helper-free stocks of these viruses induced MAIDS. Using in situ hybridization and immunocytochemistry and Southern analysis, we found that most infected cells belong to the B-cell lineage. Transformation of these B cells appears to be the primary event responsible for the development of immunodeficiency. This animal model may be relevant to our understanding of AIDS, of the immunodeficiencies associated with B-cell lymphoproliferative disorders, and of the role of B-cell proliferation and transformation in the effects of superantigens, since Pr60gag appears to be a superantigen.

Peyer's Patches in Murine AIDS: Dissociation Between Lymphoproliferation and Anergy

“…Therefore, lymphoproliferation and anergy are not necessarily associated in MAIDS; (4) the absence of lymphoproliferation in this organ is not due to an absence of the defective virus in the organ as demonstrated by PCR. Furthermore B220 dim B cells previously described as corresponding to infected B cells [2] were observed in the PP of the infected mice; and (5) PP HEV from infected animals have a normal expression of MAdCAM-1. Moreover, LN and PP lymphocytes from infected mice have an increased expression of the a4 integrin.…”

“…(1) PP undergo a striking atrophy during MAIDS, mostly due to B cell depletion, while the proportion of CD4 + and CD8 + T cells is increased; (2) in sharp contrast with the dramatic phenotypic shift taking place in LN, the frequency of T cells with a memory/ activated phenotype and lacking Thy-1 expression is not increased in the PP of the infected mice; (3) despite the absence of lymphoproliferation, T cells from infected PP present striking functional defects in comparison to normal mice. Therefore, lymphoproliferation and anergy are not necessarily associated in MAIDS; (4) the absence of lymphoproliferation in this organ is not due to an absence of the defective virus in the organ as demonstrated by PCR.…”

“…Adult C57BL/6 mice infected with a mixture of murine leukaemia viruses (MuLVs) termed RadLV-Rs develop a progressive lymphoproliferative disease associated with profound immunodeficiency [1]. Although the causative agent of the disease, a defective retrovirus, infects mostly B cells [2,3], CD4 + T cells can also be infected [4] and are absolutely required to sustain the lymphoproliferative process involving B cells in peripheral lymphoid organs [5]. Furthermore, CD4 + T cells also develop functional as well as phenotypical abnormalities such as the loss of membrane expression of Thy-1 [6,7].…”

Mice transgenic for a soluble form of murine cytotoxic T lymphocyte antigen 4 are refractory to murine acquired immune deficiency sydrome development

“…Phenotypic abnormalities associated with MAIDS include the expansion of large B cells expressing B220 at low density, 6 and the expansion of the Thy-1.2 ± CD4 + subset. 23,24 At the 13th week,¯uorescence-activated cell sorter (FACS) analysis con®rmed these phenotypic shifts in each LN suspension from non-transgenic infected mice (not shown).…”

“…The syndrome is characterized by a rapid and persistent proliferation of B and CD4 + T cells, hypergammaglobulinaemia, phenotypic abnormalities of lymphocyte subsets, and increasingly severe defects of cellular and humoral immunity. 5 Although B cells are the main target for defective viral expression, 6 development of the disease is strictly dependent on the presence of functional CD4 + T cells. 7 Mechanisms involved in CD4 + T-cell contribution to MAIDS pathogenesis have been only partly elucidated.…”