Vaginal transmission of HIV-1 in hu-SCID mice: a new model for the evaluation of vaginal microbicides

Fabio, Simonetta Di; Giannini, Giacomo; Lapenta, Caterina; Spada, Massimo; Binelli, Andrea; Germinario, Elena; Sestili, Paola; Belardelli, Filippo; Proietti, Enrico; Vella, Stefano

doi:10.1097/00002030-200111230-00003

Cited by 41 publications

(23 citation statements)

References 22 publications

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“…However, our results strongly suggest that T lymphocytes cross the mucosal barrier and very rapidly disseminate in host tissues, including distant lymphoid tissues, where they can transmit infection to resident cells. Similarly, donor lymphocytes and monocyte/macrophages migrating across the cervico-vaginal mucosa and to distal lymphoid tissues have been reported in mouse models of reproductive physiology and infection [19][20][21][22].…”

Section: Discussionmentioning

confidence: 71%

Infection of Macaques after Vaginal Exposure to Cell‐Associated Simian Immunodeficiency Virus

et al. 2010

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Section: Discussionmentioning

confidence: 71%

Infection of Macaques after Vaginal Exposure to Cell‐Associated Simian Immunodeficiency Virus

et al. 2010

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“…Recently, Di Fabio et al (14) reported on the vaginal transmission of HIV-1 in hu-SCID mice as a new model for the evaluation of vaginal microbicides. This model turned out to be particularly useful to test the activity of compounds against cell-associated HIV, and therefore, should be highly relevant for the evaluation of compounds such as the lectins.…”

Section: Discussionmentioning

confidence: 99%

Mannose-Specific Plant Lectins from the Amaryllidaceae Family Qualify as Efficient Microbicides for Prevention of Human Immunodeficiency Virus Infection

Balzarini

Hatse

Vermeire

et al. 2004

Antimicrob Agents Chemother

147

131

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The plant lectins derived from Galanthus nivalis (Snowdrop) (GNA) and Hippeastrum hybrid (Amaryllis) (HHA) selectively inhibited a wide variety of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains and clinical (CXCR4-and CCR5-using) isolates in different cell types. They also efficiently inhibited infection of T lymphocytes by a variety of mutant virus strains. GNA and HHA markedly prevented syncytium formation between persistently infected HUT-78/HIV cells and uninfected T lymphocytes. The plant lectins did not measurably affect the antiviral activity of other clinically approved anti-HIV drugs used in the clinic when combined with these drugs. Short exposure of the lectins to cell-free virus particles or persistently HIV-infected HUT-78 cells markedly decreased HIV infectivity and increased the protective (microbicidal) activity of the plant lectins. Flow cytometric analysis and monoclonal antibody binding studies and a PCR-based assay revealed that GNA and HHA do not interfere with CD4, CXCR4, CCR5, and DC-SIGN and do not specifically bind with the membrane of uninfected cells. Instead, GNA and HHA likely interrupt the virus entry process by interfering with the virus envelope glycoprotein. HHA and GNA are odorless, colorless, and tasteless, and they are not cytotoxic, antimetabolically active, or mitogenic to human primary T lymphocytes at concentrations that exceed their antivirally active concentrations by 2 to 3 orders of magnitude. GNA and HHA proved stable at high temperature (50°C) and low pH (5.0) for prolonged time periods and can be easily formulated in gel preparations for microbicidal use; they did not agglutinate human erythrocytes and were not toxic to mice when administered intravenously.

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“…Progesterone is frequently used in vaginal infection models to synchronize estrous cycles and to increase susceptibility by thinning out the vaginal layer, including models of simian immunodeficiency virus/SHIV infection in nonhuman primates (13,14,67,69,70,78) and mouse models of HIV-1 (68,79), human papillomavirus (HPV) (80), and herpes simplex virus 2 (HSV-2) (81) infection. Increased susceptibility to viral infection after mucosal N-9 application has been described in models of HPV infection (80) and both vaginal and rectal HSV-2 infection (72,82,83).…”

Section: Discussionmentioning

confidence: 99%

Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model

Gruell

Bournazos

Ravetch

et al. 2013

J Virol

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The development of an effective vaccine preventing HIV-1 infection remains elusive. Thus, the development of novel approaches capable of preventing HIV-1 transmission is of paramount importance. However, this is partly hindered by the lack of an easily accessible small-animal model to rapidly measure viral entry. Here, we report the generation of a human CD4-and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo. We show that antibodies and antiretrovirals mediate preexposure protection in this mouse model and that the serum antibody concentration required for protection from cervicovaginal infection is comparable to that required to protect macaques. Our results suggest that this system represents a model for the preclinical evaluation of prophylactic or vaccine candidates. It further supports the idea that broadly neutralizing antibodies should be evaluated for use as preexposure prophylaxis in clinical trials.

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Vaginal transmission of HIV-1 in hu-SCID mice: a new model for the evaluation of vaginal microbicides

Abstract: Because of its simplicity and practical features compared with other animal models, the vaginal HIV-infected hu-SCID mouse model may prove useful to test the activity of compounds against cell-associated HIV and, possibly, other sexually transmitted diseases.

Cited by 41 publications

References 22 publications

Infection of Macaques after Vaginal Exposure to Cell‐Associated Simian Immunodeficiency Virus

Infection of Macaques after Vaginal Exposure to Cell‐Associated Simian Immunodeficiency Virus

Mannose-Specific Plant Lectins from the Amaryllidaceae Family Qualify as Efficient Microbicides for Prevention of Human Immunodeficiency Virus Infection

Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model

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