Article

Wu L, KewalRamani VN.Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 6:859-868

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 12/2006; 6(11):859-68. DOI: 10.1038/nri1960
Source: PubMed

ABSTRACT

Dendritic cells (DCs) are crucial for the generation and the regulation of adaptive immunity. Because DCs have a pivotal role in marshalling immune responses, HIV has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Defining the mechanisms that underlie cell-cell transmission of HIV and understanding the role of DCs in this process should help us in the fight against HIV infection. This Review highlights the latest advances in our understanding of the interactions between DCs and HIV, focusing on the mechanisms of DC-mediated viral dissemination.

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    • "epithelium can support productive HIV-1 infection in vivo is controversial. It is known that these myeloid cells can sample antigens in the mucosa, capture the virus and transfer virus to susceptible CD4 þ T cells (Ballweber et al., 2011; Hu et al., 2004; Wu and KewalRamani, 2006). Furthermore, macrophages in the mucosa express the HIV-1 receptor CD4 and co-receptor CCR5, but their role in the initial events of HIV-1 infection is yet to be defined (Shen et al., 2009; Wira et al., 2005). "
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    ABSTRACT: Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Aug 2015 · Virology
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    • "As a result, propagation of persistent infection along with GALT damage leads eventually to bacterial translocation into the systemic circulation[120,129,130]. Finally, this leads to persistent systemic immune activation and enhancement of viral replication, two major hallmarks of disease progression (Fig. 1)[120,129,130]. These findings illustrate how this smart virus infects GALT and induces translocation of bacterial load from the lumen of gastrointestinal tract (GIT) into the blood which in turn can complicate the disease. "
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    ABSTRACT: HIV-1 infection is a major public health problem and an important cause of death among adults. In light of innate immune system being the first, rapid and nonspecific response, this highlights the importance of exploiting the active arms of innate immunity to eradicate the invader and triggering a more specific immune response, the adaptive immune system. Each type of cells in the innate immune system has a unique distribution and function in the body and therefore differs in their ability to induce adaptive immune arms according to the stimuli. Any functional defect or alteration in the innate immune system can affect the adaptive arms of the immune system in terms of failure to overcome the battlefield with the invader. This review focuses on the relevant function of each member of the innate immune system and sheds the light on detailed mechanisms about how this smart virus invades and evades the immune system which opens new insights into the immunology and therapeutic targeting of HIV-1 infection.
    Full-text · Article · Aug 2015 · HIV and AIDS Review
    • "Dysregulation of DCs occurs during the course of HIV-1 disease (Sabado et al., 2010). Moreover, the early events in HIV-1–host interactions are likely to make critical contributions to disease progression (Neil and Bieniasz, 2009; Wu and KewalRamani, 2006). Vpr protein, which is enclosed within HIV-1 virions and is capable of causing cell cycle arrest in CD4 + T cells (Poon et al., 1998), is one of the HIV-1 proteins encountered by host cells during the early stage of infection (Cohen et al., 1990; Poon et al., 1998). "
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    ABSTRACT: Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that directly link the innate and adaptive immune responses. HIV-1 infection of DCs leads to a diverse array of changes in gene expression and play a major role in dissemination of the virus into T-cells. Although HIV-1 Vpr is a pleiotropic protein involved in HIV-1 replication and pathogenesis, its exact role in APCs such as DCs remains elusive. In this study, utilizing a microarray-based systemic biology approach, we found that HIV-1 Vpr differentially regulates (fold change > 2.0) more than 200 genes, primarily those involved in the immune response and innate immune response including type I interferon signaling pathway. The differential expression profiles of select genes involved in innate immune responses (interferon-stimulated genes [ISGs]), including MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, and TNFSF10, were validated by real-time quantitative PCR; the results were consistent with the microarray data. Taken together, our findings are the first to demonstrate that HIV-1 Vpr induces ISGs and activates the type I IFN signaling pathway in human DCs, and provide insights into the role of Vpr in HIV-1 pathogenesis. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jun 2015 · Virus Research
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