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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
"It is known that Treg plays a crucial role in the maintenance of immune homeostasis . In CCR5-tropic HIV-1-infected mice, Vpr-dependent depletion of Treg resulted in immune activation , which is a hallmark in the patients infected with HIV-1 . Altogether, these findings suggest that Vpr enhances CCR5-tropic but not CXCR4-tropic HIV-1 replication mediating G2 arrest and apoptosis in vivo by exploiting Treg during the acute phase of infection. "
[Show abstract][Hide abstract]ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) encodes four accessory genes: vif, vpu, vpr, and nef. Recent investigations using in vitro cell culture systems have shed light on the roles of these HIV-1 accessory proteins, Vif, Vpr, Vpu, and Nef, in counteracting, modulating, and evading various cellular factors that are responsible for anti-HIV-1 intrinsic immunity. However, since humans are the exclusive target for HIV-1 infection, conventional animal models are incapable of mimicking the dynamics of HIV-1 infection in vivo. Moreover, the effects of HIV-1 accessory proteins on viral infection in vivo remain unclear. To elucidate the roles of HIV-1 accessory proteins in the dynamics of viral infection in vivo, humanized mouse models, in which the mice are xenotransplanted with human hematopoietic stem cells, has been utilized. This review describes the current knowledge of the roles of HIV-1 accessory proteins in viral infection, replication, and pathogenicity in vivo, which are revealed by the studies using humanized mouse models.
"One important observation in this regard is that there are low levels of CCR5 coreceptor expression on central memory CD4 T cells in natural SIV hosts[11,29,48].Paiardini et al.demonstrated that central memory CD4 T cells in sooty mangabey resist CCR5 upregulation following activation and were relatively resistant to infection both in vivo and in vitro. Thus, restricted and delayed expression of CCR5 on activated CD4 T cells may preserve the homeostasis of the pool of " resting " naïve and memory CD4 T cells while supporting high levels of virus production in activated effector CD4 cells that are likely to die as a consequence of activation-induced cell death. "
[Show abstract][Hide abstract]ABSTRACT: Simian immunodeficiency virus (SIV)-infected natural hosts do not progress to clinical acquired immune deficiency syndrome yet display high viral replication and an acute immunologic response similar to pathogenic SIV/human immunodeficiency virus infections. During chronic SIV infection, natural hosts suppress their immune activation, whereas pathogenic hosts display a highly activated immune state. Here, we review natural host SIV infections with an emphasis on different immune cell subsets and their potential roles in suppressing immune activation during the chronic phase that contributes to the nonpathogenic outcome of these infections.
"In contrast to experimental infections of Asian macaques (Macaca mulatta) with SIV, infections in natural hosts (African nonhuman primates; ie, sooty mangabeys, African green monkeys , and mandrills) are nonpathogenic  . While both pathogenic and nonpathogenic SIV infections are similar in the extent of viral replication and cytopathy, there is an absence of systemic chronic immune activation in nonpathogenic infections of natural hosts . Factors that contribute to immune activation in HIV-1–infected individuals can be of viral origin, such as Env, Nef, Tat, and Vpr, a consequence of an ineffective resolution of antiviral innate and adaptive immune responses and/or increased permeability of the gastrointestinal epithelium to microbial products, which result in activation of the innate immune responses and enhanced production of proinflammatory cytokines, such as IFN-α, TNF-α, interleukin 1, and interleukin 6 . "
[Show abstract][Hide abstract]ABSTRACT: Sexual transmission of human immunodeficiency virus type 1 (HIV-1) occurs across mucosal surfaces of the genital and gastrointestinal
tracts and accounts for the vast majority of newly acquired infections worldwide. In the absence of an effective vaccine,
interventional strategies such as microbicides that target viral attachment and entry into mucosa-resident target cells are
particularly attractive and might have the greatest impact on reducing the HIV-1 pandemic. Rational development of microbicides
would be greatly aided with a better understanding of several key questions of mucosal HIV-1 transmission, including the molecular
mechanism(s) of how HIV-1 traverses mucosal barriers, the type of cells that it initially infects to gain a foothold in the
naive host, and how it is disseminated from local sites of infection to draining lymph nodes. In this review, we discuss the
role of myeloid dendritic cells (DCs) in cell-associated HIV-1 transmission and in facilitating systemic HIV-1 dissemination.
We will evaluate the role of CD169 as a DC-associated HIV-1 attachment factor, investigate the molecular mechanisms by which
HIV-1 particles are transferred from DCs to CD4+ T cells across virological synapses, and provide arguments for inclusion of molecules in microbicides that can effectively
target HIV-1 attachment to DCs and DC-mediated virus transfer.
Full-text · Article · Dec 2014 · The Journal of Infectious Diseases