scholarly journals Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1120 ◽  
Author(s):  
Sara Dizzell ◽  
Aisha Nazli ◽  
Gregor Reid ◽  
Charu Kaushic
Keyword(s):  
Epithelial Cells ◽  
Protective Effect ◽  
Sex Hormones ◽  
Proinflammatory Cytokines ◽  
Barrier Function ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Probiotic Lactobacilli ◽  
Hiv 1 ◽  
Female Genital

Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.

scholarly journals Mechanisms of Endogenous HIV-1 Reactivation by Endocervical Epithelial Cells

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Germán G. Gornalusse ◽  
Rogelio Valdez ◽  
Gabriella Fenkart ◽  
Lucia Vojtech ◽  
Lamar M. Fleming ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex ◽  
Epithelial Cells ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Tnf Α ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Hiv 1 ◽  
Female Genital

ABSTRACT Pharmacological HIV-1 reactivation to reverse latent infection has been extensively studied. However, HIV-1 reactivation also occurs naturally, as evidenced by occasional low-level viremia (“viral blips”) during antiretroviral treatment (ART). Clarifying where blips originate from and how they happen could provide clues to stimulate latency reversal more effectively and safely or to prevent viral rebound following ART cessation. We studied HIV-1 reactivation in the female genital tract, a dynamic anatomical target for HIV-1 infection throughout all disease stages. We found that primary endocervical epithelial cells from several women reactivated HIV-1 from latently infected T cells. The endocervical cells’ HIV-1 reactivation capacity further increased upon Toll-like receptor 3 stimulation with poly(I·C) double-stranded RNA or infection with herpes simplex virus 2 (HSV-2). Notably, acyclovir did not eliminate HSV-2-induced HIV-1 reactivation. While endocervical epithelial cells secreted large amounts of several cytokines and chemokines, especially tumor necrosis factor alpha (TNF-α), CCL3, CCL4, and CCL20, their HIV-1 reactivation capacity was almost completely blocked by TNF-α neutralization alone. Thus, immunosurveillance activities by columnar epithelial cells in the endocervix can cause endogenous HIV-1 reactivation, which may contribute to viral blips during ART or rebound following ART interruption. IMPORTANCE A reason that there is no universal cure for HIV-1 is that the virus can hide in the genome of infected cells in the form of latent proviral DNA. This hidden provirus is protected from antiviral drugs until it eventually reactivates to produce new virions. It is not well understood where in the body or how this reactivation occurs. We studied HIV-1 reactivation in the female genital tract, which is often the portal of HIV-1 entry and which remains a site of infection throughout the disease. We found that the columnar epithelial cells lining the endocervix, the lower part of the uterus, are particularly effective in reactivating HIV-1 from infected T cells. This activity was enhanced by certain microbial stimuli, including herpes simplex virus 2, and blocked by antibodies against the inflammatory cytokine TNF-α. Avoiding HIV-1 reactivation could be important for maintaining a functional HIV-1 cure when antiviral therapy is stopped.

scholarly journals Selenium Deficiency Is Associated With Shedding of HIV-1–Infected Cells in the Female Genital Tract

2001 ◽  
Vol 26 (4) ◽  
pp. 360-364 ◽  
Author(s):  
Jared M. Baeten ◽  
Sara B. Mostad ◽  
Martin P. Hughes ◽  
Julie Overbaugh ◽  
Daniel D. Bankson ◽  
...  
Keyword(s):  
Genital Tract ◽  
Female Genital Tract ◽  
Selenium Deficiency ◽  
Infected Cells ◽  
Hiv 1 ◽  
Female Genital

HIV-1 infection and the female genital tract

The Lancet ◽  
1996 ◽  
Vol 348 (9019) ◽  
pp. 59-60 ◽  
Author(s):  
Basil Donovan
Keyword(s):  
Genital Tract ◽  
Female Genital Tract ◽  
Hiv 1 ◽  
Female Genital

scholarly journals A Human Immunodeficiency Virus (HIV)–Inducing Factor from the Female Genital Tract Activates HIV‐1 Gene Expression through the κB Enhancer

1998 ◽  
Vol 178 (5) ◽  
pp. 1343-1351 ◽  
Author(s):  
Lena Al‐Harthi ◽  
Gregory T. Spear ◽  
Farhad B. Hashemi ◽  
Alan Landay ◽  
Beverly E. Sha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Female Genital

Hormonal influence on HIV-1 transmission in the female genital tract: New insights from systems biology

2018 ◽  
Vol 80 (2) ◽  
pp. e13019
Author(s):  
Haley A. Dupont ◽  
Jeff Lam ◽  
Matthew W. Woods ◽  
Mohammed A. Zahoor ◽  
Charu Kaushic
Keyword(s):  
Systems Biology ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Hormonal Influence ◽  
Hiv 1 ◽  
Female Genital

scholarly journals Immunohistochemical localization of P-glycoprotein in adult human ovary and female genital tract of patients with benign gynecological conditions.

1990 ◽  
Vol 38 (11) ◽  
pp. 1677-1681 ◽  
Author(s):  
C L Finstad ◽  
P E Saigo ◽  
S C Rubin ◽  
M G Federici ◽  
D M Provencher ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Ovarian Surface Epithelium ◽  
Cytotoxic Agents ◽  
Surface Epithelium ◽  
Positive Staining ◽  
Multidrug Resistance Gene ◽  
P Glycoprotein ◽  
Female Genital

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein, which mediates active cellular efflux of certain cytotoxic agents. Two mouse monoclonal antibodies (MAb), C219 and JSB-1, were used to identify P-glycoprotein in frozen tissue from the female genital tract of 14 women with benign gynecological conditions; multiple samples from several sites in the genital tract were available from seven patients. P-glycoprotein was detected in the ovarian surface epithelium in four of 14 cases, in the Fallopian tube in three of five cases, in occasional epithelial cells of the endometrial glands in two of five cases, in some endocervical glandular epithelium in three of five cases, in ectocervical squamous epithelium in one of the two cases, and in luteinized cells of the eight cases in which a corpus luteum was present in the specimen. Positive staining with these two MAb was also observed in some endothelial cells in the cortex of the ovary and in the stromal tissue of the myometrium, endometrium, and endocervix. These studies suggest that, if epithelial ovarian cancers are derived from the surface epithelial cells of the ovary, a small proportion of the cancers might be expected to retain the phenotype found in non-cancerous cells and to express P-glycoprotein.

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