Cell-Associated Mucosal HIV Transmission.
J Infect Dis. 2014 Dec 15;210 Suppl 3:S605
Authors: Barre-Sinoussi F
PMID: 25414412 [PubMed - in process]
Cell-Associated HIV Mucosal Transmission: The Neglected Pathway.
J Infect Dis. 2014 Dec 15;210 Suppl 3:S606-8
Authors: Anderson DJ, Le Grand R
This supplement to The Journal of Infectious Diseases is devoted to the important and understudied topic of cell-associated human immunodeficiency virus Type 1 (HIV) mucosal transmission. It stems from a workshop held in Boston, Massachusetts, in October 2013, in which scientists discussed their research and insights regarding cell-associated HIV mucosal transmission. The 10 articles in this supplement present the case for cell-associated HIV transmission as an important element contributing to the HIV epidemic, review evidence for the efficacy of current HIV prevention strategies against cell-associated HIV transmission and opportunities for further development, and describe in vitro, ex vivo, and animal cell-associated transmission models that can be used to further elucidate the molecular mechanisms of cell-associated HIV mucosal transmission and test HIV prevention strategies. We hope that these articles will help to inform and invigorate the HIV prevention field and contribute to the development of more-effective vaccine, treatment, and microbicide strategies for HIV prevention.
PMID: 25414413 [PubMed - in process]
Characteristics and Quantities of HIV Host Cells in Human Genital Tract Secretions.
J Infect Dis. 2014 Dec 15;210(suppl 3):S609-S615
Authors: Politch JA, Marathe J, Anderson DJ
Human immunodeficiency virus (HIV)-infected leukocytes have been detected in genital secretions from HIV-infected men and women and may play an important role in the sexual transmission of HIV. However, they have been largely overlooked in studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candidates. This article describes the characteristics and quantities of leukocytes in male and female genital secretions under various conditions and also reviews evidence for the involvement of HIV-infected cells in both horizontal and vertical cell-associated HIV transmission. Additional research is needed in this area to better target HIV prevention strategies.
PMID: 25414414 [PubMed - as supplied by publisher]
Vaginal Microbiota and Sexually Transmitted Infections That May Influence Transmission of Cell-Associated HIV.
J Infect Dis. 2014 Dec 15;210(suppl 3):S616-S621
Authors: Cone RA
Vaginal microbiota and sexually transmitted infections (STIs) are likely to influence the transmission of cell-associated human immunodeficiency virus (HIV). Lactic acid produced by Lactobacillus-dominated microbiota (Nugent score 0-3) will likely inhibit transmission, especially female-to-male transmission. In contrast, polymicrobial microbiota (Nugent score 4-10), community state types IV-A and IV-B, and STIs will likely increase transmission of cell-associated HIV.
PMID: 25414415 [PubMed - as supplied by publisher]
Origins of HIV-infected Leukocytes and Virions in Semen.
J Infect Dis. 2014 Dec 15;210(suppl 3):S622-S630
Authors: Houzet L, Matusali G, Dejucq-Rainsford N
Although semen is the principal vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the infected leukocytes and free viral particles in this body fluid remain elusive. Here we review the accumulated evidence of the genital origin of HIV in semen from therapy naive individuals and men receiving suppressive highly active antiretroviral therapy (HAART), summarize the data on the detection and localization of HIV/SIV within the male genital tract, discuss the potential involvement of each genital tissue as a source of infected cells and virions in semen in the absence and presence of HAART, and suggest further studies. Deciphering the exact sources of HIV in semen will be crucial to improving HIV transmission prevention strategies.
PMID: 25414416 [PubMed - as supplied by publisher]
The Role of Cell-Associated Virus in Mother-to-Child HIV Transmission.
J Infect Dis. 2014 Dec 15;210(suppl 3):S631-S640
Authors: Milligan C, Overbaugh J
Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) continues to contribute to the global burden of disease despite great advances in antiretroviral (ARV) treatment and prophylaxis. In this review, we discuss the proposed mechanisms of MTCT, evidence for cell-free and cell-associated transmission in different routes of MTCT, and the impact of ARVs on virus levels and transmission. Many population-based studies support a role for cell-associated virus in transmission and in vitro studies also provide some support for this mode of transmission. However, animal model studies provide proof-of-principle that cell-free virus can establish infection in infants, and studies of ARVs in HIV-infected pregnant women show a strong correlation with reduction in cell-free virus levels and protection. ARV treatment in MTCT potentially provides opportunities to better define the infectious form of virus, but these studies will require better tools to measure the infectious cell reservoir.
PMID: 25414417 [PubMed - as supplied by publisher]
CD169-Dependent Cell-Associated HIV-1 Transmission: A Driver of Virus Dissemination.
J Infect Dis. 2014 Dec 15;210(suppl 3):S641-S647
Authors: Gummuluru S, Ramirez NG, Akiyama H
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.
PMID: 25414418 [PubMed - as supplied by publisher]
Modeling Mucosal Cell-Associated HIV Type 1 Transmission in Vitro.
J Infect Dis. 2014 Dec 15;210(suppl 3):S648-S653
Authors: Anderson DJ
Human immunodeficiency virus type 1 (HIV-1) can efficiently spread by direct cell-to-cell contact, a mechanism termed cell-associated HIV transmission. By some estimates, cell-associated HIV transmission is 10-1000-fold more effective than cell-free HIV infection. Mucosal cell-associated HIV transmission may occur when HIV-bearing cells in mucosal secretions from an HIV-infected donor transfer virus directly to recipient target cells in or below the mucosal epithelium, or through HIV transcytosis across the mucosal epithelium of a noninfected host. This mechanism may play an important role in the sexual and vertical transmission of HIV-1, yet most in vitro tests of vaccine and microbicide efficacy assess cell-free virus transmission. This article reviews in vitro assays that have been used to model mucosal cell-associated transmission, including microscopy, immune cell cocultures, use of HIV-infected cells in epithelial cell transcytosis assays, and cell-associated infection of mucosal tissue explants. Assays that authentically simulate mucosal cell-associated HIV transmission could provide valuable insight into mechanisms and molecules that can potentially be targeted for HIV prevention, as well as critical models for testing novel HIV prevention strategies for efficacy against cell-associated HIV transmission.
PMID: 25414419 [PubMed - as supplied by publisher]
Cell-Associated Transmission of HIV Type 1 and Other Lentiviruses in Small-Animal Models.
J Infect Dis. 2014 Dec 15;210(suppl 3):S654-S659
Authors: Moench TR
Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers.
PMID: 25414420 [PubMed - as supplied by publisher]
Nonhuman Primate Models for Cell-Associated Simian Immunodeficiency Virus Transmission: The Need to Better Understand the Complexity of HIV Mucosal Transmission.
J Infect Dis. 2014 Dec 15;210(suppl 3):S660-S666
Authors: Bernard-Stoecklin S, Gommet C, Cavarelli M, Le Grand R
Nonhuman primates are extensively used to assess strategies to prevent infection from sexual exposure to human immunodeficiency virus (HIV) and to study mechanisms of mucosal transmission. However, although semen represents one of the most important vehicles for the virus, the vast majority of preclinical challenge studies have used cell-free simian immunodeficiency virus (SIV) or simian/human immunodeficiency virus (SHIV) viral particles inoculated as diluted culture supernatants. Semen is a complex body fluid containing many factors that may facilitate or decrease HIV infectiousness. The virus in semen is present in different forms: as free virus particles or as cell-associated virus (ie, within infected leukocytes). Although cell-to-cell transmission of HIV is highly efficient, the role of cell-associated virus in semen has been surprisingly poorly investigated in nonhuman primate models. Mucosal exposure of macaques to cell-associated SIV by using infected peripheral blood mononuclear cells or spleen cells has been shown to be an efficient means of infection; however, it has yet to be shown that SIV- or SHIV-infected seminal leukocytes can transmit infection in vivo. Improvement of animal models to better recapitulate the complex microenvironment at portals of HIV entry is needed for testing candidate antiretrovirals, microbicides, and vaccines.
PMID: 25414421 [PubMed - as supplied by publisher]