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Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue.

Hu, Q; Frank, I; Williams, V; Santos, JJ; Watts, P; Griffin, GE; Moore, JP; Pope, M; Shattock, RJ (2004) Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. Journal of Experimental Medicine, 199 (8). pp. 1065-1075. ISSN 0022-1007 https://doi.org/10.1084/jem.20022212
SGUL Authors: Griffin, George Edward Hu, Qinxue Shattock, Robin John

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Abstract

Identification of cellular factors involved in HIV-1 entry and transmission at mucosal surfaces is critical for understanding viral pathogenesis and development of effective prevention strategies. Here we describe the evaluation of HIV-1 entry inhibitors for their ability to prevent infection of, and dissemination from, human cervical tissue ex vivo. Blockade of CD4 alone or CCR5 and CXCR4 together inhibited localized mucosal infection. However, simultaneous blockade of CD4 and mannose-binding C-type lectin receptors including dendritic cell-specific intercellular adhesion molecule-grabbing integrin was required to inhibit HIV-1 uptake and dissemination by migratory cells. In contrast, direct targeting of HIV-1 by neutralizing mAb b12 and CD4-IgG2 (PRO-542) blocked both localized infection and viral dissemination pathways. Flow cytometric analysis and immunostaining of migratory cells revealed two major populations, CD3(+)HLA-DR(-) and CD3(-)HLA-DR(+) cells, with a significant proportion of the latter also expressing dendritic cell-specific intercellular adhesion molecule-grabbing integrin. Bead depletion studies demonstrated that such HLA-DR(+) cells accounted for as much as 90% of HIV-1 dissemination. Additional studies using immature monocyte-derived dendritic cells demonstrated that although mannose-binding C-type lectin receptors and CD4 are the principal receptors for gp120, other mechanisms may account for virus capture. Our identification of the predominant receptors involved in HIV-1 infection and dissemination within human cervical tissue highlight important targets for microbicide development.

Item Type: Article
Additional Information: ©2004 Hu et al. Journal of Experimental Medicine. 199:1065-1075. doi: 10.1084/jem.20022212
Keywords: Antigens, CD4, CCR5 Receptor Antagonists, CD4-Positive T-Lymphocytes, Cervix Uteri, Dendritic Cells, Female, HIV Infections, HIV-1, Humans, In Vitro Techniques, Neutralization Tests, Receptors, CXCR4, Receptors, HIV, Cervix Uteri, Dendritic Cells, CD4-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, Receptors, CCR5, Receptors, CXCR4, Receptors, HIV, Antigens, CD4, Neutralization Tests, Female, AIDS, mucosa, transmission, dendritic cells, microbicide, Antigens, CD4, CCR5 Receptor Antagonists, CD4-Positive T-Lymphocytes, Cervix Uteri, Dendritic Cells, Female, HIV Infections, HIV-1, Humans, In Vitro Techniques, Neutralization Tests, Receptors, CXCR4, Receptors, HIV, Science & Technology, Life Sciences & Biomedicine, Immunology, Medicine, Research & Experimental, Research & Experimental Medicine, IMMUNOLOGY, MEDICINE, RESEARCH & EXPERIMENTAL, AIDS, mucosa, transmission, dendritic cells, microbicide, IMMUNODEFICIENCY-VIRUS TYPE-1, DC-SIGN, DENDRITIC CELLS, GENITAL-TRACT, SEXUAL TRANSMISSION, MONOCLONAL-ANTIBODY, CCR5 ANTAGONIST, SMALL-MOLECULE, EXPRESSION, MACROPHAGES, Immunology, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Journal of Experimental Medicine
ISSN: 0022-1007
Language: eng
Dates:
DateEvent
19 April 2004Published
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
AI52048National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
R01 AI40877National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
R21 AI52060National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
PubMed ID: 15078900
Web of Science ID: WOS:000221039100004
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URI: https://openaccess.sgul.ac.uk/id/eprint/107657
Publisher's version: https://doi.org/10.1084/jem.20022212

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