Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses

Abstract

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-y) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with

Cryptococcus neoformans infection in mice previously infected with LP-BM5 MuLV, the agent of murine AIDS (MAIDS)

“…Spleen and inguinal lymph node weights in co-infected mice were markedly reduced compared to mice infected with the virus only. This phenomenon had been described in models of co-infection with LP-BM5 MuLV and Toxoplasma godii [18,19] and Leishmania major [32]. In contrast to the study by Gazzinelli et al [IS], we found no change in the ecotropic viral load, or in Con A-induced spleen cell proliferation in vitro.…”

“…Another possibility is that MAIDS, which is responsible for the increased expression of some proinflammatory cytokines [27,28], could accentuate the inflammatory response to C. neoformans, resulting in increased mortality through pulmonary and cerebral oedema. 18 22…”

“…This is why it seems preferable to reserve the use of LP-BMS MuLV for studies of cellular pathology associated with retroviral infection rather than studies of opportunistic infections. Some studies with LP-BM5 MuLV infection have shown no particular susceptibility to AIDSassociated opportunistic pathogens such as Mycobacterium avium complex [31], or reactivation of infections such as toxoplasmosis [18,19] and leishmaniasis [32].…”

“…On the basis of the link between T helper cell-derived cytokines and MAIDS progression, it has been postulated that the inhibitory effect of Toxoplusma on the development of MAIDS is due to parasite-induced Thl cytokine production [18,19]. However, ascribing the progression of MAIDS to the ThllTh2 balance seems somewhat simplistic [32].…”

HIV‐1 infection: new treatment paradigms

“…The report published in this issue of the European Journal of Clinical Investigation [24] provides additional evidence that combination of anti-inflammatory, antiretroviral and lympholytic therapies may lead to total viral suppression and restoration of immune function in a murine model of AIDS. Infection of mice with retroviral complex LP-BM5 leads to profound immunodeficiency, characterized by impaired T-and B-cell responses to mitogens, polyclonal B-cell activation, hypergammaglobulinemia, enhanced susceptibility to secondary infections, and the emergence of lymphomas due to the development of anergy [25]. Fraternale and colleagues treated LP-BM5 infected animals with GSH-loaded erythrocytes (antioxidant effect) and the reverse transcriptase inhibitor AZT (antiviral effect), or this combination alternating with fludarabine.…”