Human Immunodeficiency Virus Type 1 Infection of Human Uterine Epithelial Cells: Viral Shedding and Cell Contact–Mediated Infectivity

Asin, Susana; Wildt-Perinic, Dunja; Mason, Sarah I; Howell, Alexandra L.; Wira, Charles R.; Fanger, Michael W.

doi:10.1086/374782

Cited by 24 publications

(16 citation statements)

References 49 publications

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“…Uterine epithelial cells and stromal fibroblasts infected with an X4-tropic strain of HIV-1 supported RT and integration of HIV-1, transcription of viral DNA, and viral release. Although the levels of virus that were released from cultures of either epithelial cells or stromal fibroblasts were relatively low, they were within the range of values that have been reported for epithelial cell lines of intestinal, vaginal, endometrial, or fibroblastoid origin [5,6,[29][30][31][32][33][34][35]. Furthermore, the secreted virus was infectious to a CD4 + T cell line (H9 cells).…”

Section: Discussionsupporting

confidence: 58%

“…Identifying the cell population initially infected within the female reproductive tract (FRT) and the putative mechanisms by which HIV-1 is disseminated to distal sites is important to our understanding of the pathogenesis of HIV-1. Moreover, defining the mechanisms and conditions that either promote or inhibit HIV-1 infection within the FRT is necessary for the design and development of preventative measures.Studies to identify cell populations within the FRT that become infected have focused on cell lines or primary cells and tissues from the lower FRT [5,6]. …”

mentioning

confidence: 99%

“…We previously reported that endometrial cell lines [6] and uterine primary cells [7] are susceptible to HIV-1 infection. To further investigate the possibility that uterine epithelial cells and stromal fibroblasts are primary sites for HIV-1 infection, we performed a systematic analysis of replication of HIV-1 in these cell populations.…”

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confidence: 99%

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Transmission of HIV‐1 by Primary Human Uterine Epithelial Cells and Stromal Fibroblasts

Asin¹,

Fanger²,

Wildt-Perinic³

et al. 2004

J INFECT DIS

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Women can become infected with human immunodeficiency virus type 1 (HIV-1) after the heterosexual transmission of virus from an infected male partner. To understand the events that result in transmission of HIV-1 across the female reproductive tract, we characterized the life-cycle events of HIV-1 in primary cultures of human uterine epithelial cells and stromal fibroblasts. Epithelial cells and stromal fibroblasts released virus particles after exposure to either X4-or R5-tropic strains of HIV-1. Virus released by these cells was able to infect CD4 + T cells. When exposed to an X4-tropic strain of HIV-1, these cells supported HIV-1 reverse transcription, integration, and viral DNA transcription. When exposed to an R5-tropic strain, however, these cells released unmodified virus. These data suggest that uterine cells are targets for productive infection with X4-tropic strains and release unmodified R5-tropic viruses that would then be able to infect submucosal target cells, including T cells and macrophages.Although heterosexual transmission is the predominant mechanism by which women acquire HIV-1 infection [1][2][3][4], our knowledge about the viral and host factors that lead to infection is limited. Identifying the cell population initially infected within the female reproductive tract (FRT) and the putative mechanisms by which HIV-1 is disseminated to distal sites is important to our understanding of the pathogenesis of HIV-1. Moreover, defining the mechanisms and conditions that either promote or inhibit HIV-1 infection within the FRT is necessary for the design and development of preventative measures.Studies to identify cell populations within the FRT that become infected have focused on cell lines or primary cells and tissues from the lower FRT [5,6].

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

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Transmission of HIV‐1 by Primary Human Uterine Epithelial Cells and Stromal Fibroblasts

Asin¹,

Fanger²,

Wildt-Perinic³

et al. 2004

J INFECT DIS

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“…Epithelial cell infection by HIV is inefficient but occurs through several CD4-independent mechanisms (Phillips and Bourinbaiar, 1992). Likewise, HIV can transiently infect epithelial and stromal cells of the endometrium, with notable differences in HIV receptor expression and cytotoxic T-lymphocyte activity by menstrual phase and menopause status (Howell et al, 1997;Asin et al, 2003;Yeaman et al, 2003). Anti-HIV medications would likely reduce HIV replication and perhaps allow cell proliferation, either directly or indirectly Bettaccini et al, 2005;Chung et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Risk of breast, ovary, and uterine corpus cancers among 85 268 women with AIDS

et al. 2006

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By linking HIV/AIDS and cancer surveillance data in 12 US regions, breast and reproductive cancer risks with AIDS were compared to those in the general population. Trends in standardized incidence ratios (SIRs) were assessed by CD4 count, AIDS-relative time, and calendar time. Standardized incidence ratios were indirectly adjusted for cancer risk factors using data from AIDS cohort participants and the general population. With AIDS, 313 women developed breast cancer (SIR 0.69, 95% confidence interval (CI) 0.62 -0.77), 42 developed ovary cancer (SIR 1.05, 95% CI, 0.75 -1.42), and 31 developed uterine corpus cancer (SIR 0.57, 95% CI, 0.39 -0.81). Uterine cancer risk was reduced significantly after age 50 (SIR 0.33). Breast cancer risk was reduced significantly both before (SIR 0.71) and after (SIR 0.66) age 50, and was lower for local or regional (SIR 0.54) than distant (SIR 0.89) disease. Breast cancer risk varied little by CD4 count (P trend ¼ 0.47) or AIDS-relative time (P trend ¼ 0.14) or after adjustment for established cancer risk factors. However, it increased significantly between 1980 and 2002 (P trend ¼ 0.003), approaching the risk of the general population. We conclude that the cancer deficit reflected direct or indirect effects of HIV/AIDS and that anti-HIV therapy reduced these effects. Increasing numbers of women have been infected with human immunodeficiency virus (HIV) and now are living with the acquired immunodeficiency syndrome (AIDS). The effects of AIDS on women, particularly in the era of highly active antiretroviral therapy (HAART), are not well defined. In the era before HAART, the risks of developing Kaposi sarcoma, anal cancer, and perhaps lymphoma were lower for women than for men with AIDS (Beral and Newton, 1998;Goedert, 2000). Other than cervical cancer, no differences by gender have been reported for the few other malignancies found in excess among people with AIDS (PWA) (Goedert et al, 1998;Frisch et al, 2001).Breast cancer may occur less often in women with AIDS than in the general population (Goedert et al, 1998;Frisch et al, 2001). Ovary and uterine corpus cancers have not been associated with AIDS or other immune deficiencies, but weak associations or susceptible subgroups may have been overlooked because these malignancies are relatively rare. No previous study has evaluated the effects of improving anti-HIV therapies or whether differences in cancer incidence might merely reflect differences in known risk factors for cancer.Using population-based data, we have investigated whether the risk of breast, ovary, or uterine corpus cancers differ for women with AIDS, whether breast cancer risk differs with increasing severity or duration of immune deficiency, or with increasing availability and efficacy of anti-HIV therapies; also whether menopause or selected risk factors modify or explain any associations. MATERIALS AND METHODS Detection and definition of cancersFrom 2003 through 2005, we linked HIV/AIDS and cancer registration data (including name, race, sex, dates of birth and de...

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“…Our more recent studies have focused on the susceptibility to HIV infections of uterine epithelium cell lines to investigate the mechanisms of HIV-1 replication [19]. These cell lines, RL95-2, ECC1, and Hec-1a, all expressed low levels of CD4 and Gal-C, in addition to CXCR4, but did not express CCR5.…”

Section: Introductionmentioning

confidence: 99%

HIV-1 infection of the female reproductive tract

Howell

Asin²,

Yeaman³

et al. 2005

Curr HIV/AIDS Rep

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The human immunodeficiency virus type 1 (HIV-1) infects cells within mucosal tissues, including those of the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not completely understood. We performed phenotypical analyses and infectivity studies of primary FRT cells to identify potential targets of infection within the FRT. Our findings indicate that expression of HIV-1 receptors and coreceptors in the FRT varies as a function of menstrual-cycle stage, suggesting that sex hormone levels may influence a woman's susceptibility to infection by HIV-1. Moreover, HIV-1 strains that utilize the CXCR4 chemokine receptor for infectivity are able to undergo reverse transcription, integration, viral DNA transcription, and viral release, whereas viral strains that utilize CCR5 do not undergo these early replicative events, and are only released unmodified from these cells. This indicates that several mechanisms for viral infection and transmission are present throughout the FRT.

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Human Immunodeficiency Virus Type 1 Infection of Human Uterine Epithelial Cells: Viral Shedding and Cell Contact–Mediated Infectivity

Cited by 24 publications

References 49 publications

Transmission of HIV‐1 by Primary Human Uterine Epithelial Cells and Stromal Fibroblasts

Transmission of HIV‐1 by Primary Human Uterine Epithelial Cells and Stromal Fibroblasts

Risk of breast, ovary, and uterine corpus cancers among 85 268 women with AIDS

HIV-1 infection of the female reproductive tract

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