Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells

Ceballos, Ana; Lenicov, Federico Remes; Sabatté, Juan; Rodrígues, Christian Rodríguez; Cabrini, Mercedes; Jancic, Carolina; Raiden, Silvina; Donaldson, M.J.; Pasqualini, Rodolfo Agustín; Marı́n-Briggiler, Clara I.; Vazquez‐Levin, Mónica H.; Capani, Francisco; Amigorena, Sébastian; Geffner, Jorge

doi:10.1084/jem.20091579

Cited by 96 publications

(66 citation statements)

References 79 publications

(152 reference statements)

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“…In addition to entry receptors, viruses subvert a wide variety of molecules expressed on the cell surface as viral attachment receptors; among these, HSPG, ␣4␤7 integrin, and the C-type lectins DC-SIGN and DCIR (also known as CLEC4A) have been shown to bind to HIV-1 gp120 (8,(32)(33)(34). Heparan sulfate was recently demonstrated to be a novel attachment receptor for Nipah virus to mediate viral binding and spread (35).…”

Section: Purification Of Mast Cells From Human Intestinal Mucosamentioning

confidence: 99%

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Jiang

Wei

et al. 2016

J Virol

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Despite great advances in antiretroviral therapies, human immunodeficiency virus type 1 (HIV-1) infection still remains a major global epidemic. Sexual transmission is the principal route of HIV-1 acquisition, making the genital and rectal mucosae the major sites of viral transmission. The intestinal mucosa is also the primary site where HIV-1 amplifies to disseminate virus throughout the host and is critical in the early events in the establishment of infection and evasion of immune defenses. However, the mechanisms contributing to the establishment of HIV-1 primary infection remain largely unexplored. Cell-associated viral dissemination has been proposed to play pivotal roles in HIV-1 primary infection, and multiple cell types, such as dendritic cells (DCs) and macrophages, have been reported to be hijacked by HIV-1 for local and systemic viral spread (1-4). DCs provide one of the best-described cell models for understanding cell-mediated HIV-1 capture and dissemination (1,(5)(6)(7)(8).Mast cells are derived from hematopoietic progenitor cells and undergo final maturation in vascularized tissues. Mast cells are strategically in close contact with the host-environment interface, such as the skin, airway, gastrointestinal tract, and urinary tract. They express numerous pathogen-associated molecular patterns and play an important role in the early immunosurveillance for many pathogens (9, 10). Mast cells can interact with various immune cells in complex ways, including release of soluble factors and direct contact (11), and are important immune effector and modulatory cells that help to link innate and adaptive immunity in the fight against pathogens (9,(12)(13)(14). They have been shown to be important for host defense against various viruses, such as vesicular stomatitis virus, Sendai virus, hantavirus, reovirus, dengue virus, influenza virus, herpes simplex virus, and murine cytomegalovirus (15-23). Additionally, mast cells can serve as antigenpresenting cells and participate in traditional immunologic synapse formation with T cells to mediate antigen-specific T cell activation (24).

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Section: Purification Of Mast Cells From Human Intestinal Mucosamentioning

confidence: 99%

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Jiang

Wei

et al. 2016

J Virol

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“…To achieve this goal, we preincubated irradiated monocytes and lymphocytes with blocking antibodies at 10 g/ml or pretreated the irradiated cells with a mixture of heparinases I, II, and III (10 U/ml) (14,21).…”

Section: Resultsmentioning

confidence: 99%

“…Shown are means and SEM of six replicates. cell surfaces that have been identified as a major source of HIV binding in epithelial cells (21), spermatozoa (14), and leukocytes, including monocytes and lymphocytes (28)(29)(30); reviewed in references 31 and 32).…”

Section: Discussionmentioning

confidence: 99%

“…Monocytes and basophils are not the only cell types that capture HIV at their surfaces and transfer it to target cells, as it was shown that both human genital epithelial cells and spermatozoa capture HIV-1 through HS and efficiently transmit the virus (14,21). Whether HIV is transmitted to dendritic cells (DCs) or T cells (14,21) or to TZM-bl cells, as in our study, cell-cell contact is required for an efficient transfer of HIV from donor to target cells.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, whether virus attached to the surfaces of seminal cells of HIV-infected individuals can transfer HIV infection is not clear. Since many of the seminal cells express various HIV receptors or express a wide variety of surface molecules involved in HIV attachment (2,12,13), there are reasons to consider these cells vehicles for HIV sexual transmission from an infected male to his uninfected partner, as has been suggested with regard to spermatozoa (14).…”

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Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human TissueEx Vivo

Barreto-de-Souza

Arakelyan

Zicari

et al. 2016

J Virol

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Unprotected sexual intercourse with HIV-infected men is the major cause of new infections. HIV virions are released into semen by various cells of the male genital tract, as well as by infected monocytes and lymphocytes present in semen. Some of these virions may attach to the surfaces of cells, infected or uninfected. We investigated whether cells carrying attached HIV on their surfaces can transmit infection. We addressed this question in a model system of human tissue exposed ex vivo to monocytes and lymphocytes carrying HIV on their surfaces. We gamma irradiated the cells to prevent their productive infection. In spite of comparable amounts of HIV attached to monocytes and lymphocytes, only monocytes were capable of transmitting infection and triggering productive infection in tissue. This HIV-1 transmission was mediated by cell-cell contacts. Our experiments suggest that in vivo, HIV attached to infected or uninfected monocytes, which far outnumber lymphocytes in HIV-infected semen, may contribute to sexual transmission of HIV from men to their partners. T ransmission of human immunodeficiency virus (HIV) occurs mainly through unprotected sexual intercourse, in which seminal HIV is deposited on rectal or vaginal mucosa (1-3). The probability of HIV transmission positively correlates with the viral load in semen and varies from 1/200 to 1/2,000 for male-to-female transmission and from 1/10 to 1/1,600 for male-to-male transmission (4). In semen, HIV exists in different forms: (i) free-floating viral particles, (ii) viruses in infected cells (in particular monocytes and lymphocytes [5-8]), and (iii) viral particles that after being released by infected cells reattached to the surfaces of cells, infected or uninfected.Earlier, it was shown that both cell-free HIV and infected cells are capable of transmitting infection in ex vivo models and in nonhuman primates (9, 10), although the relative contributions of these two pools to HIV transmission remain a matter of debate (reviewed in references 6 and 11). In particular, whether virus attached to the surfaces of seminal cells of HIV-infected individuals can transfer HIV infection is not clear. Since many of the seminal cells express various HIV receptors or express a wide variety of surface molecules involved in HIV attachment (2, 12, 13), there are reasons to consider these cells vehicles for HIV sexual transmission from an infected male to his uninfected partner, as has been suggested with regard to spermatozoa (14).Here, we address this question by comparing tissue infections ex vivo with cell-free HIV and with cell-attached HIV. In particular, we investigated whether HIV adsorbed at the surfaces of lymphocytes or monocytes, two major types of cells present in the semen of infected individuals, can transmit infection to human tissue ex vivo. We found that in this model, only HIV attached to monocytes, but not that attached to lymphocytes, was able to transmit infection, and the transmitted virus replicated in the recipient tissue similarly to cell-free ...

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Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa

Jadhav

Velhal

Deshpande

et al. 2011

Journal of Medical Virology

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The presence of distinct viral variants in different cells and secretions of the same person influences the transmission of HIV as well as the response to the host defense and to therapy. Sperm-associated virus is also a risk factor for sexual transmission of HIV. Characterization of the C2-V3 region of HIV1C env gene by the Heteroduplex Mobility Assay (HMA) and sequencing demonstrated the presence of distinct variants in the peripheral blood mononuclear cells (PBMCs) and the sperm of the same individual (n = 6). The translated amino acid sequences of HIV variants in the PBMCs of all the study participants (n = 12) and spermatozoa of the six participants characterized showed the presence of distinct variants with different numbers of N-linked glycosylation (NLG) sites. Infectivity of PBMCs of these persons by co-culture with PBMCs from healthy individuals as detected by the p24 levels in the culture supernatant did not show a correlation with the blood plasma viral load. Interestingly, the infectivity of the sperm samples from four of the five individuals showed positive correlation with the viral load in seminal plasma. The study suggests the presence of distinct viral variants in the sperm and PBMCs of the same person with differential infectivity, and the NLG sites may be associated with the affinity of HIV to receptor/co-receptor usages as well as affinity toward neutralizing antibodies which may influence the risk of sperm associated virus in sexual transmission of HIV and transmit the virus further to distal cells.

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Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells

Cited by 96 publications

References 79 publications

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human TissueEx Vivo

Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa

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Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells

Cited by 96 publications

References 79 publications

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 + T Cells

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 + T Cells

Monocytes but Not Lymphocytes Carrying HIV-1 on Their Surface Transmit Infection to Human TissueEx Vivo

Characterization of human immunodeficiency virus (HIV1C) variants in peripheral blood mononuclear cells and spermatozoa

Contact Info

Product

Resources

About

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells

Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans -Infection of CD4 ⁺ T Cells