scholarly journals Female Genital Tract Shedding of CXCR4-Tropic HIV Type 1 Is Associated with a Majority Population of CXCR4-Tropic HIV Type 1 in Blood and Declining CD4+Cell Counts

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

2007 ◽  
Vol 49 (4) ◽  
pp. 231-233 ◽  
Author(s):  
Jorge Casseb ◽  
Maria Paulina Posada-Vergara ◽  
Patrícia Montanheiro ◽  
Lígia Maria Ichii Fukumori ◽  
Ingrid Olah ◽  
...  

INTRODUCTION: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4+ cell counts, thus rendering this parameter useless as an AIDS-defining event. OBJECTIVE: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4+ cells. MATERIAL AND METHODS: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB) or polymerase chain reaction (PCR). All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO) classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC) classification of 1988. The first T CD4+ cells count available before starting anti-retroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. RESULTS: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4+ cell counts was 189 (98-688) cells/mm³ and 89 (53-196) cells/mm³ for co-infected subjects who had an AIDS-defining event, and HIV-only infected individuals, respectively (p = 0.036). Eight of 27 co-infected subjects (30%) were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4+ cell counts at the time of their AIDS- defining event. DISCUSSION: Our results indicate that higher T CD4+ cells count among HIV-1/HTLV-1-coinfected subjects was found in 12% of the patients who presented an AIDS-defining event. These subjects also showed a TSP/HAM simile picture when it was the first manifestation of disease; this incidence is 20 times higher than that for HTLV-1-only infected subjects in endemic areas.


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 ◽  
...  

2000 ◽  
Vol 182 (2) ◽  
pp. 459-466 ◽  
Author(s):  
Aggrey O. Anzala ◽  
J. Neil Simonsen ◽  
Joshua Kimani ◽  
T. Blake Ball ◽  
Nico J. D. Nagelkerke ◽  
...  

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

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