Nonprogressive and Progressive Primate Immunodeficiency Lentivirus Infections

Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
Immunity (Impact Factor: 21.56). 06/2010; 32(6):737-42. DOI: 10.1016/j.immuni.2010.06.004
Source: PubMed


Natural hosts for simian immunodeficiency virus (SIV) can be, and are often naturally, infected with species-specific SIVs, but do not develop acquired immunodeficiency syndrome (AIDS). These natural hosts maintain high SIV viral loads, but avoid immunodeficiency. Elucidating the mechanisms that allow natural hosts to coexist with SIV without overt disease may provide crucial information for understanding AIDS pathogenesis. Over the past few years, several key features of natural SIV infections have been described in studies conducted predominantly in sooty mangabeys (SMs), African green monkeys (AGMs), and mandrills. Natural SIV hosts are able to avoid the chronic, generalized immune system activation that is associated with disease progression in HIV-infected individuals and are known to downmodulate the expression of the receptors for SIV. In this perspective we propose that a critical factor that differentiates nonprogressive from progressive HIV or SIV infection is the maintenance of T cell immune competence in the face of a virus that infects and kills CD4(+) T cells. Elucidation of the mechanisms underlying the preservation of immune function during and after the acute phase of natural SIV infection may lead to the design of novel preventive and therapeutic interventions for treatment of chronic HIV infection.

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    • "The early dynamics of SIV replication have also been studied in the African green monkeys, mandrills, and sooty mangabeys (Diop et al. 2000; Kornfeld et al. 2005; Onanga et al. 2006). SIV infection in these natural hosts is typically nonpathogenic despite persistent high viral loads (due to robust virus replication), and results in a substantial preservation of the immune system function, lack of chronic immune activation , and a lifespan similar to SIV-uninfected individuals (Brenchley et al. 2010; Paiardini et al. 2009). Interestingly, in both natural and non-natural hosts there is initially a robust innate immune response to the virus. "
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    ABSTRACT: Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV–AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts.
    International Journal of Primatology 03/2014; 35(2). DOI:10.1007/s10764-014-9763-7 · 1.99 Impact Factor
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    • "Chronic immune activation is a characteristic feature of HIV-1 infection contributing to CD4+ T cell loss and progression to AIDS and death [1-3]. In contrast, SIV infection of natural primate hosts does not cause chronic immune activation despite sustained systemic viral replication and thus disease progression and immunodeficiency are largely absent [4-6]. Persistent immune activation is characterized by elevated levels of serum cytokines and chemokines [7-9], B cell dysregulation (reviewed in [10]), interference with T cell homeostasis [11,12] and lymphocyte activation, reflected by expression of markers such as CD38 and HLA-DR [3,13], increased in vivo turnover [14,15] and enhanced spontaneous apoptosis [16]. "
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    ABSTRACT: Background HIV infection induces chronic immune activation which is associated with accelerated disease progression; the causes of this activation, however, are incompletely understood. We investigated the activation status of CD4+ T cells specific for chronic herpes viruses and the non-persistent antigen tetanus toxoid (TT) in HIV positive and HIV negative donors to assess whether persistent infections contribute to chronic CD4+ T cell activation. Methods Untreated HIV+ patients and healthy, aged matched controls were recruited and activation levels assessed and compared between cells specific for persistent and non-persistent antigens. Activation levels on antigen-specific CD4+ T cells were measured by intracellular cytokine staining following in vitro stimulation with various recall antigens (CMV, EBV, HSV, VZV and TT) in conjunction with cell surface phenotyping. Results Activation levels of herpes virus-specific CD4+ T cell populations, assessed by co-expression of CD38 and HLA-DR, were significantly elevated in HIV+ individuals compared to normal controls and compared to TT-specific responses. In contrast, we found similar levels of activation of TT-specific CD4+ T cells in HIV+ and HIV- donors. Conclusions These results show a disparate distribution of immune activation within CD4+ T cell populations depending on their specificity and suggest that the elevated level of immune activation that characterizes chronic HIV infection may be influenced by the persistence of other antigens.
    BMC Infectious Diseases 02/2013; 13(1):100. DOI:10.1186/1471-2334-13-100 · 2.61 Impact Factor
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    • "In contrast to the RM model where SIV infection results in AIDS, nonpathogenic or natural SIV hosts exist, including the SM and the AGM among others. Natural hosts are endemically infected with SIV with high levels of viral replication and yet they have a life span similar to uninfected animals, as they do not develop immunode fi ciency, immune activation, or AIDS (Paiardini et al. 2009 ; Brenchley et al. 2010 ; Jacquelin et al. 2009 ) . Transcriptional pro fi ling in pathogenic and nonpathogenic SIV-infected primates reveals differences in IFN a responses, where both hosts have strong IFN a response signatures during acute infection, but only the pathogenically infected animals that go on to develop AIDS maintain elevated IFN a response signatures over the course of chronic infection (Jacquelin et al. 2009 ; Manches and Bhardwaj 2009 ) . "
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    ABSTRACT: Plasmacytoid dendritic cells (pDCs) are innate immune cells that are specialized to produce interferon-alpha (IFNα) and participate in activating adaptive immune responses. Although IFNα inhibits HIV-1 (HIV) replication in vitro, pDCs may act as inflammatory and immunosuppressive dendritic cells (DCs) rather than classical antigen-presenting cells during chronic HIV infection in vivo, contributing more to HIV pathogenesis than to protection. Improved understanding of HIV-pDC interactions may yield potential new avenues of discovery to prevent HIV transmission, to blunt chronic immune activation and exhaustion, and to enhance beneficial adaptive immune responses. In this chapter we discuss pDC biology, including pDC development from progenitors, trafficking and localization of pDCs in the body, and signaling pathways involved in pDC activation. We focus on the role of pDCs in HIV transmission, chronic disease progression and immune activation, and immunosuppression through regulatory T cell development. Lastly, we discuss potential future directions for the field which are needed to strengthen our current understanding of the role of pDCs in HIV transmission and pathogenesis.
    Advances in Experimental Medicine and Biology 01/2013; 762:71-107. DOI:10.1007/978-1-4614-4433-6_3 · 1.96 Impact Factor
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