Current Immunology Reviews (Discontinued) - Volume 15, Issue 1, 2019

Most new HIV infections, over 80%, occur through sexual transmission. During sexual transmission, the virus must bypass specific female and male reproductive tract anatomical barriers to encounter viable target cells. Understanding the generally efficient ability of these barriers to exclude HIV and the precise mechanisms of HIV translocation beyond these genital barriers is essential for vaccine and novel therapeutic developme Read More

The transmission of HIV is generally inefficient. Despite the development of a diverse viral quasispecies in a chronically infected individual, a severe genetic bottleneck is observed during transmission, leading to only one or a few genetic variants establishing infection. This genetic bottleneck is the result of both stochastic events and selection pressures, such that viruses with specific traits are favored during transmission. This c Read More

The mucosal surfaces of the genital and gastrointestinal tracts are the routes by which HIV-1 is acquired, excluding persons infected parenterally. Identification of the mucosal target cells and the receptors by which HIV-1 enters these cells is fundamental to elucidating the biology of HIV-1 transmission. The mucosal target cells include epithelial cells, dendritic cells, Langerhans cells, CD4+ T-cells, macrophages and even ma Read More

Because HIV is sexually transmitted, there is considerable interest in defining the nature of anti-HIV immunity in the female reproductive tract (FRT) and in developing ways to elicit antiviral immunity in the FRT through vaccination. Although it is assumed that the mucosal immune system of the FRT is of central importance for protection against sexually transmitted diseases, including HIV, this arm of the immune system has only Read More

The mucosal immune systems of the genital and intestinal tracts are considered as the most frequent sites of HIV-1 entry, displaying remarkable immunological differences in the systemic immune compartment which must be considered in the evaluation of humoral and cellular immune responses to HIV- 1. Marked differences in the fluids from the genital and intestinal tracts and in plasma with respect to the Ig isotypes, t Read More

The protective function of mucosal HIV-1- or SIV-specific antibodies against viral infection has stimulated extensive studies of their Ig isotype association with differences in specificity and in effector functions. In contrast to many mucosally acquired microbial infections in which the humoral responses are dominated by induction of secretory IgA (S-IgA), HIV-1/SIV infections stimulate vigorous IgG responses in sera as Read More

As our understanding of mucosal immunity increases, it is becoming clear that the host response to HIV-1 is more complex and nuanced than originally believed. The mucosal landscape is populated with a variety of specialized cell types whose functions include combating infectious agents while preserving commensal microbiota, maintaining barrier integrity, and ensuring immune homeostasis. Advances in multiparameter f Read More

Among the most significant findings in the pathogenesis of HIV infection was the discovery that almost total depletion of intestinal CD4+ T cells occurs rapidly after SIV or HIV infection, regardless of the route of exposure, and long before CD4+ T cell losses occur in blood or lymph nodes. Since these seminal discoveries, we have learned much about mucosal and systemic CD4+ T cells, and found several key differences be Read More

Immune protection in the female reproductive tract (FRT) has evolved to meet the challenges of sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and an immunologically distinct semi-allogeneic fetus. Throughout the FRT, the innate immune system is essential for the recognition and initial response to incoming pathogens. Key mediators of innate immune protection examined in this review include epit Read More

Optimal protective immunity to HIV will likely require that plasma cells, memory B cells and memory T cells be stationed in mucosal tissues at portals of viral entry. Mucosal vaccine administration is more effective than parenteral vaccine delivery for this purpose. The challenge has been to achieve efficient vaccine uptake at mucosal surfaces, and to identify safe and effective adjuvants, especially for mucosally administered Read More

Passive immunization has been used since the late 1800’s to prevent and treat human infectious diseases. Administration of animal immune sera and human immunoglobulin has given way to the use of monoclonal antibodies (mAbs) for passive immunization, and highly potent broadly neutralizing anti-HIV antibodies (bNAbs) are now being considered for HIV therapy and prophylaxis. Recent studies have shown that syst Read More

Increased availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas has proven remarkably successful at reducing HIV vertical transmission rates over the past several decades. Yet, still, more than 170,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence. Mother-to-child transmission (MTCT) of HIV-1 can occur at one of several distinct st Read More

HIV-1 is present in many secretions including oral, intestinal, genital, and breast milk. However, most people exposed to HIV-1 within these mucosal compartments do not become infected despite often frequent and repetitive exposure over prolonged periods of time. In this review, we discuss what is known about the levels of cell-free HIV RNA, cell-associated HIV DNA and cellassociated HIV RNA in external secretions. Levels of Read More