Immunodeficiency lentiviral infections in natural and non-natural hosts

Brenchley, Jason M.; Paiardini, Mirko

doi:10.1182/blood-2010-12-325936

Cited by 46 publications

(36 citation statements)

References 101 publications

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“…32 Interestingly, the level of cell-associated SIV DNA in TCMs is about one log lower in sooty mangabeys as compared to rhesus macaques while the level of infection in effector memory cells is comparable. This finding is consistent with earlier work by several groups working with the pathogenic macaque model, in which disease progression was linked to depletion of the TCM pool.…”

Section: Immune Activation In Viral Infectionmentioning

confidence: 99%

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Plaeger

Collins

Musib

et al. 2012

AIDS Research and Human Retroviruses

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With the advent of highly effective antiretroviral therapy (ART), infection with human immunodeficiency virus (HIV) has become a chronic disease rather than a death sentence. Nevertheless, effectively treated individuals have a higher than normal risk for developing noninfectious comorbidities, including cardiovascular and renal disease. Although traditional risk factors of aging as well as treatment toxicity contribute to this risk, many investigators consider chronic HIV-associated inflammation a significant factor in such end-organ disease. Despite effective viral suppression, chronic inflammation persists at levels higher than in uninfected people, yet the stimuli for the inflammation and the mechanism by which inflammation persists and promotes disease pathology remain incompletely understood. This critical gap in scientific understanding complicates and hampers effective decision making about appropriate medical intervention. To better understand the mechanism(s) of chronic immune activation in treated HIV disease, three questions need answers: (1) what is the cause of persistent immune activation during treated HIV infection, (2) what are the best surrogate markers of chronic immune activation in this setting, and (3) what therapeutic intervention(s) could prevent or reverse this process? The NIH sponsored and convened a meeting to discuss the state of knowledge concerning these questions and the best course for developing effective therapeutic strategies. This report summarizes the findings of that NIH meeting.

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Section: Immune Activation In Viral Infectionmentioning

confidence: 99%

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Plaeger

Collins

Musib

et al. 2012

AIDS Research and Human Retroviruses

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“…SIVs are at the origin of the human immunodeficiency virus (HIV) pandemic, with HIV type 1 (HIV-1) and HIV-2 arising from cross-species transmission from chimpanzees/gorillas and sooty mangabeys, respectively (4)(5)(6). Yet, while HIV infection is highly pathogenic and progresses to generalized immunodeficiency and AIDS, SIVs are generally believed to be nonpathogenic in their natural hosts (7)(8)(9)(10), with only a few cases of progression to AIDS being reported thus far in African NHP species (11). However, the nonpathogenicity of SIVs in their natural hosts was concluded from the study of only a few host species (African green monkeys [AGMs], sooty mangabeys, and mandrills), and the vast majority of these studies were performed on captive monkeys (12)(13)(14)(15)(16)(17)(18)(19).…”

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confidence: 99%

Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild

Jasinska

Feyertag

et al. 2014

J Virol

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African green monkeys (AGMs) are naturally infected with simian immunodeficiency virus (SIV) at high prevalence levels and do not progress to AIDS. Sexual transmission is the main transmission route in AGM, while mother-to-infant transmission (MTIT) is negligible. We investigated SIV transmission in wild AGMs to assess whether or not high SIV prevalence is due to differences in mucosal permissivity to SIV (i.e., whether the genetic bottleneck of viral transmission reported in humans and macaques is also observed in AGMs in the wild). We tested 121 sabaeus AGMs (Chlorocebus sabaeus) from the Gambia and found that 53 were SIV infected (44%). By combining serology and viral load quantitation, we identified 4 acutely infected AGMs, in which we assessed the diversity of the quasispecies by single-genome amplification (SGA) and documented that a single virus variant established the infections. We thus show that natural SIV transmission in the wild is associated with a genetic bottleneck similar to that described for mucosal human immunodeficiency virus (HIV) transmission in humans. Flow cytometry assessment of the immune cell populations did not identify major differences between infected and uninfected AGM. The expression of the SIV coreceptor CCR5 on CD4 ؉ T cells dramatically increased in adults, being higher in infected than in uninfected infant and juvenile AGMs. Thus, the limited SIV MTIT in natural hosts appears to be due to low target cell availability in newborns and infants, which supports HIV MTIT prevention strategies aimed at limiting the target cells at mucosal sites. Combined, (i) the extremely high prevalence in sexually active AGMs, (ii) the very efficient SIV transmission in the wild, and (iii) the existence of a fraction of multiparous females that remain uninfected in spite of massive exposure to SIV identify wild AGMs as an acceptable model of exposed, uninfected individuals. IMPORTANCEWe report an extensive analysis of the natural history of SIVagm infection in its sabaeus monkey host, the African green monkey species endemic to West Africa. Virtually no study has investigated the natural history of SIV infection in the wild. The novelty of our approach is that we report for the first time that SIV infection has no discernible impact on the major immune cell populations in natural hosts, thus confirming the nonpathogenic nature of SIV infection in the wild. We also focused on the correlates of SIV transmission, and we report, also for the first time, that SIV transmission in the wild is characterized by a major genetic bottleneck, similar to that described for HIV-1 transmission in humans. Finally, we report here that the restriction of target cell availability is a major correlate of the lack of SIV transmission to the offspring in natural hosts of SIVs.

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“…CD4 ϩ TCM cells are self-renewing cells that proliferate to maintain long-term stability of the CD4 ϩ T cell compartment (8). In the context of SIV infection of RMs, CD4 ϩ TCM cells undergo a striking increase in proliferation that is thought to represent, at least in part, an attempt to maintain CD4 ϩ T cell homeostasis by compensating for the cell loss due to both direct virus infection and chronic immune activation (21,22).…”

Section: Resultsmentioning

confidence: 99%

“…CD4 ϩ T cells are critical in enhancing both cellular and humoral immune responses that can effectively suppress virus replication, yet their activation makes these cells more susceptible to infection by HIV, thus creating more targets for virus replication (2,3). In marked contrast to HIV-infected humans, and despite similar viral loads, natural simian immunodeficiency virus (SIV) hosts, such as sooty mangabeys (SMs) and African green monkeys (AGMs), generally maintain healthy CD4 ϩ T cell levels and avoid chronic immune activation, thus remaining AIDS free (4)(5)(6)(7)(8)(9)(10). Comparing and contrasting the mechanisms of CD4 ϩ T cell homeostasis in natural hosts for SIV to those in experimentally SIV-infected rhesus macaques (RMs), which progress to AIDS, may provide important insights into the mechanisms of disease progression in HIV-infected humans.…”

Section: T He Precise Factors Determining the Rate Of Cd4mentioning

confidence: 99%

Increased Stability and Limited Proliferation of CD4 ⁺ Central Memory T Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus Macaques

McGary¹,

Cervasi²,

Chahroudi³

et al. 2014

J Virol

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Depletion of CD4 ؉ central memory T (TCM) cells dictates the tempo of progression to AIDS in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs IMPORTANCE Comparison of the immunologic effects of simian immunodeficiency virus (SIV) infection on rhesus macaques (RMs), a speciescharacterized by progression to AIDS, and natural host sooty mangabeys (SMs), a species which remains AIDS free, has become a useful tool for identifying mechanisms of human immunodeficiency virus (HIV) disease progression. One such distinguishing feature is that CD4 ؉ central memory T (TCM) cells in SIV-infected SMs are less infected than the same cells in RMs. Here we investigated whether lower levels of infection in SMs translate into a better-preserved CD4 ؉ TCM compartment. We found that the CD4 ؉ TCM compartment is significantly more stable in SIV-infected SMs. Likely to compensate for this cell loss, we also found that CD4 ؉ TCM cells increase their level of proliferation upon SIV infection in RMs but not in SMs, which mechanistically supports their preferential infectivity. Our study provides new insights into the importance of long-term maintenance of CD4 ؉ TCM homeostasis during HIV/SIV infection.

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Immunodeficiency lentiviral infections in natural and non-natural hosts

Cited by 46 publications

References 101 publications

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild

Increased Stability and Limited Proliferation of CD4 ⁺ Central Memory T Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus Macaques

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Immunodeficiency lentiviral infections in natural and non-natural hosts

Cited by 46 publications

References 101 publications

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Factors Associated with Siman Immunodeficiency Virus Transmission in a Natural African Nonhuman Primate Host in the Wild

Increased Stability and Limited Proliferation of CD4 + Central Memory T Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus Macaques

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Increased Stability and Limited Proliferation of CD4 ⁺ Central Memory T Cells Differentiate Nonprogressive Simian Immunodeficiency Virus (SIV) Infection of Sooty Mangabeys from Progressive SIV Infection of Rhesus Macaques