scholarly journals HIV Type 1 and Cytomegalovirus Coinfection in the Female Genital Tract

2004 ◽  
Vol 190 (3) ◽  
pp. 619-623 ◽  
Author(s):  
Nell S. Lurain ◽  
Emmanuel S. Robert ◽  
Jiahong Xu ◽  
Margaret Camarca ◽  
Alan Landay ◽  
...  
2012 ◽  
Vol 28 (11) ◽  
pp. 1524-1532 ◽  
Author(s):  
Richard E. Haaland ◽  
Sharon T. Sullivan ◽  
Tammy Evans-Strickfaden ◽  
Jeffrey L. Lennox ◽  
Clyde E. Hart

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Puja Bagri ◽  
Varun C. Anipindi ◽  
Philip V. Nguyen ◽  
Danielle Vitali ◽  
Martin R. Stämpfli ◽  
...  

ABSTRACT It is well established that interferon gamma (IFN-γ) production by CD4+ T cells is critical for antiviral immunity against herpes simplex virus 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4+ T cells in HSV-2 antiviral immunity is yet to be elucidated. Here we demonstrate that IL-17A plays an important role in enhancing antiviral T helper type 1 (Th1) responses in the female genital tract (FGT) and is essential for effective protection conferred by HSV-2 vaccination. While IL-17A did not play a critical role during primary genital HSV-2 infection, seen by lack of differences in susceptibility between IL-17A-deficient (IL-17A −/−) and wild-type (WT) C57BL/6 mice, it was critical for mediating antiviral responses after challenge/reexposure. Compared to WT mice, IL-17A −/− mice (i) infected intravaginally and reexposed or (ii) vaccinated intranasally and challenged intravaginally demonstrated poor outcomes. Following intravaginal HSV-2 reexposure or challenge, vaccinated IL-17A −/− mice had significantly higher mortality, greater disease severity, higher viral shedding, and higher levels of proinflammatory cytokines and chemokines in vaginal secretions. Furthermore, IL-17A −/− mice had impaired Th1 cell responses after challenge/reexposure, with significantly lower proportions of vaginal IFN-γ+ CD4+ T cells. The impaired Th1 cell responses in IL-17A −/− mice coincided with smaller populations of IFN-γ+ CD4+ tissue resident memory T (TRM) cells in the genital tract postimmunization. Taken together, these findings describe a novel role for IL-17A in regulating antiviral IFN-γ+ Th1 cell immunity in the vaginal tract. This strategy could be exploited to enhance antiviral immunity following HSV-2 vaccination. IMPORTANCE T helper type 1 (Th1) immunity, specifically interferon gamma (IFN-γ) production by CD4+ T cells, is critical for protection against genital herpesvirus (HSV-2) infection, and enhancing this response can potentially help improve disease outcomes. Our study demonstrated that interleukin-17A (IL-17A) plays an essential role in enhancing antiviral Th1 responses in the female genital tract (FGT). We found that in the absence of IL-17A, preexposed and vaccinated mice showed poor disease outcomes and were unable to overcome HSV-2 reexposure/challenge. IL-17A-deficient mice (IL-17A −/−) had smaller populations of IFN-γ+ CD4+ tissue resident memory T (TRM) cells in the genital tract postimmunization than did wild-type (WT) mice, which coincided with attenuated Th1 responses postchallenge. This has important implications for developing effective vaccines against HSV-2, as we propose that strategies inducing IL-17A in the genital tract may promote more effective Th1 cell immunity and better overall protection.


2005 ◽  
Vol 79 (1) ◽  
pp. 353-363 ◽  
Author(s):  
Sean Philpott ◽  
Harold Burger ◽  
Christos Tsoukas ◽  
Brian Foley ◽  
Kathryn Anastos ◽  
...  

ABSTRACT Investigation of human immunodeficiency virus type 1 (HIV-1) in the genital tract of women is crucial to the development of vaccines and therapies. Previous analyses of HIV-1 in various anatomic sites have documented compartmentalization, with viral sequences from each location that were distinct yet phylogenetically related. Full-length RNA genomes derived from different compartments in the same individual, however, have not yet been studied. Furthermore, although there is evidence that intrapatient recombination may occur frequently, recombinants comprising viruses from different sites within one individual have rarely been documented. We compared full-length HIV-1 RNA sequences in the plasma and female genital tract, focusing on a woman with high HIV-1 RNA loads in each compartment who had been infected heterosexually and then transmitted HIV-1 by the same route. We cloned and sequenced 10 full-length HIV-1 RNA genomes from her genital tract and 10 from her plasma. We also compared viral genomes from the genital tract and plasma of four additional heterosexually infected women, sequencing 164 env and gag clones obtained from the two sites. Four of five women, including the one whose complete viral sequences were determined, displayed compartmentalized HIV-1 genomes. Analyses of full-length, compartmentalized sequences made it possible to document complex intrapatient HIV-1 recombinants that were composed of alternating viral sequences characteristic of each site. These findings demonstrate that the genital tract and blood harbor genetically distinct populations of replicating HIV-1 and provide evidence that recombination between strains from the two compartments contributes to rapid evolution of viral sequence variation in infected individuals.


2000 ◽  
Vol 181 (6) ◽  
pp. 1950-1956 ◽  
Author(s):  
Stephen D. Lawn ◽  
Shambavi Subbarao ◽  
Thomas C. Wright, Jr. ◽  
Tammy Evans‐Strickfaden ◽  
Tedd V. Ellerbrock ◽  
...  

2001 ◽  
Vol 33 (6) ◽  
pp. 894-896 ◽  
Author(s):  
Susan Cu‐Uvin ◽  
Joseph W. Hogan ◽  
Angela M. Caliendo ◽  
Joseph Harwell ◽  
Kenneth H. Mayer ◽  
...  

2004 ◽  
Vol 48 (2) ◽  
pp. 632-634 ◽  
Author(s):  
Odile Launay ◽  
Michel Tod ◽  
Kamel Louchahi ◽  
Linda Belarbi ◽  
Olivier Bouchaud ◽  
...  

ABSTRACT Plasma and cervicovaginal secretion (CVS) samples were collected from 19 human immunodeficiency virus type 1-infected women on lopinavir- or indinavir-containing regimens. Lopinavir and indinavir were detectable in 29 and 93% of CVS samples, respectively, a finding that may be ascribed to these drugs' differences in protein binding and pKa. The relationship between lopinavir and indinavir pharmacodynamics and viral evolution in the female genital tract should be assessed over time.


2000 ◽  
Vol 38 (7) ◽  
pp. 2665-2669 ◽  
Author(s):  
James Bremer ◽  
Marek Nowicki ◽  
Suzanne Beckner ◽  
Donald Brambilla ◽  
Mike Cronin ◽  
...  

Human immunodeficiency virus type 1 (HIV-1) RNA levels in female genital tract and peripheral blood samples were compared using two commercial amplification technologies: the Roche AMPLICOR HIV-1 MONITOR test and either the Organon Teknika nucleic acid sequence-based amplification (NASBA-QT) assay or the NucliSens assay. Estimates of HIV-1 RNA copy number were derived from internal kit standards and analyzed unadjusted and adjusted to a common set of external standards. We found a discordance rate of approximately 18% between the two technologies for the detection of HIV-1 in either the genital tract or peripheral blood samples. Detection discordance was not consistent among specimens or among women. There were no significant differences in adjusted or unadjusted estimates of HIV-1 RNA copy number in the genital tract samples using the AMPLICOR HIV-1 MONITOR test and either the NASBA-QT assay or the NucliSens assay. In addition, the estimated HIV-1 RNA copy number in peripheral blood samples did not differ when tested with the NucliSens assay and the AMPLICOR HIV-1 MONITOR test using kit standards. However, there was a significant difference in estimated RNA copy number between the NASBA-QT assay and the AMPLICOR HIV-1 MONITOR test for internal kit standards, which, as we have previously shown, was eliminated after adjustment with the external standards. Our results suggest that the Roche and Organon Teknika assays are equivalent for quantifying HIV-1 RNA in female genital tract specimens, although variation in detection does exist.


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