Simian Immunodeficiency Virus Disease Course Is Predicted by the Extent of Virus Replication during Primary Infection

Staprans, Silvija I.; Dailey, Peter J.; Rosenthal, Ann; Horton, Chris; Grant, Robert M.; Lerche, Nicholas W.; Feinberg, Mark B.

doi:10.1128/jvi.73.6.4829-4839.1999

Cited by 110 publications

(30 citation statements)

References 86 publications

(110 reference statements)

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“…Changes in blood mDCs but not in CD4 + T cells at set-point are predictive of disease outcome Animals in this cohort were distinguished on the basis of disease progression, with one group of 11 monkeys remaining healthy until elective sacrifice at a mean of 60 weeks post-infection ('stable' group) and the other group of 10 animals succumbing to AIDS-defining illnesses at a mean of 32 weeks ('progressor' group) [53]. This differential outcome was independent of immunotherapy and was inversely proportional to virus loads at set-point, defined as the mean plasma virus titers from weeks 8-12 post-infection, consistent with previous reports [50,52]. When we monitored mDC numbers in blood in these groups of animals over the first 12 weeks of infection, we found a divergent response.…”

Section: Resultssupporting

confidence: 85%

A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques

Barratt‐Boyes

Wijewardana

2011

Journal of Medical Primatology

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Background The mechanism for loss of myeloid dendritic cells (mDCs) from the circulation in HIV-infected individuals and its relationship to disease progression is not understood. Methods A longitudinal analysis of the mDC response in blood and lymph nodes during the first 12 weeks of infection was performed in a cohort of SIVmac251-infected rhesus macaques with different disease outcomes. Results Monkeys that rapidly progressed to disease or had long-term stable infection had significant losses or increases, respectively, in blood mDCs that were inversely correlated with virus load at set-point. The loss of mDCs from progressor animals was associated with evidence of an increase in CCR7-CCL19 dependent mDC recruitment to lymph nodes and an increase in mDC apoptosis. Conclusions mDC recruitment to and death within inflamed lymph nodes may contribute to disease progression in SIV infection, whereas mobilization without increased recruitment to lymph nodes may promote disease control.

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Section: Resultssupporting

confidence: 85%

A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques

Barratt‐Boyes

Wijewardana

2011

Journal of Medical Primatology

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“…In the initial weeks of HIV infection of humans and pathogenic simian immunodeficiency virus (SIV) infection of Asian macaques, viral replication peaks, then declines to a quasiequilibrated set point of ongoing viral production and clearance, the level of which plays a major role in determining the subsequent tempo of disease progression (Mellors et al, 1996; Staprans et al, 1999). Outcomes range from an inability to substantially restrain viral replication from peak levels, leading to early immunological collapse and rapid progression to AIDS, to control of viral replication to undetectable levels and long-term nonprogression (Farzadegan et al, 1996; Picker et al, 2004; Deeks and Walker, 2007; Goulder and Watkins, 2008).…”

mentioning

confidence: 99%

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

Okoye

Park

Rohankhedkar

et al. 2009

Journal of Experimental Medicine

101

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Depletion of CD8+ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8+ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8+ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4+ effector memory T (TEM) cells and, to a lesser extent, transitional memory T (TTrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4+/CCR5+ SIV “target” cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8+ lymphocytes in SIV− RMs led to a sustained increase in the number of potential CD4+ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4+ TEM cell proliferation of CD8+ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4+ TEM and TTrM cell proliferation, it did not recapitulate the viral dynamics of CD8+ lymphocyte depletion. These data suggest that CD8+ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.

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“…Thus, only FIS-2 induced late immunosuppression without any signs of erythroleukaemia. Several studies have shown that a high level of virus in the blood after primary infection indicates a poor prognosis in complex retrovirus infections such as HIV (19,20) and SIV (21)(22)(23)(24). Furthermore, a rapid early virus dissemination has been associated with a high level of postpeak viraemia and low survival in the SIV animal model (21).…”

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confidence: 99%

Early dissemination rates of Friend murine leukaemia virus variants correlate with late pathogenesis

Bruland

Dai

Lavik

et al. 2002

APMIS

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FIS-2, a less oncogenic, immunosuppressive variant of the Friend murine leukaemia virus (F-MuLV), was used to explore whether the differences in biological features were related to early virus dissemination rates or sites of replication. We found that erythroblasts were the primary target cells for both F-MuLV and FIS-2, while B- and T-cells were infected later in the infection. Although FIS-2 replicated to similar titres as F-MuLV, we observed a delay in peak viraemia titre and in the number of virus-positive cells in bone marrow and spleen. Studies including the chimeric viruses RE3 (FIS-2LTR with a F-MuLV background) and RE4 (F-MuLV LTR with a FIS-2 background) indicated that the delay in dissemination was due to mutations in FIS-2 LTR. The kinetics for early virus replication correlated with previously reported mean latency time for virus-induced erythroleukaemia in mice inoculated as newborns and with the onset of immunosuppression in adult mice. In addition, F-MuLV-induced late immunosuppression coincided with signs of erythroleukaemia and persistent viraemia. FIS-2 induced a more moderate late immunosuppression without persistent viraemia or signs of erythroleukaemia. Overall, our findings indicated that early viral replication is a prognostic factor in murine retrovirus-induced pathogenesis.

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Simian Immunodeficiency Virus Disease Course Is Predicted by the Extent of Virus Replication during Primary Infection

Cited by 110 publications

References 86 publications

A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques

A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques

Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis

Early dissemination rates of Friend murine leukaemia virus variants correlate with late pathogenesis

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