Abstract
Chronically SHIVSF162P3N-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4+ T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4+ T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection.
Highlights
Peripheral blood CD4+ T cell counts are a clinical marker for assessing disease progression in human immunodeficiency virus (HIV)-infected patients as well as in simian immunodeficiency virus (SIV)-/simian-human immunodeficiency virus (SHIV)–infected macaques
These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys
Future investigations are necessary to identify novel and more reliable clinical markers correlated with viremia and disease progression in HIV-infected individuals
Summary
Peripheral blood CD4+ T cell counts are a clinical marker for assessing disease progression in HIV-infected patients as well as in SIV-/SHIV–infected macaques. Several lines of evidence have shown that HIV-infected patients with similar levels of viral loads and CD4+ T cell progress to AIDS at different rates, especially those on ART [5,6,7,8,9] This clinical observation in humans has been confirmed in the studies with SIV- or SHIV-infected monkey models, showing that while CD4+ T cells can be depleted for years before the animals develop AIDS [10,11,12,13]. These findings indicate that other immune components, in addition to CD4+ T cells, are involved in HIV disease progression to AIDS [8, 14]
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