Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Henning TR [original query] |
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Development of a rectal sexually transmitted infection (STI) model in Rhesus macaques using Chlamydia trachomatis serovars E and L2
Henning TR , Morris M , Ellis S , Kelley K , Phillips C , Ritter J , Jones T , Nachamkin E , Chen CY , Hong J , Kang J , Patton D , McNicholl J , Papp J , Kersh EN . J Med Primatol 2017 46 (5) 218-227 BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies. |
Increases in endogenous or exogenous progestins promote virus-target cell interactions within the non-human primate female reproductive tract
Carias AM , Allen SA , Fought AJ , Kotnik Halavaty K , Anderson MR , Jimenez ML , McRaven MD , Gioia CJ , Henning TR , Kersh EN , Smith JM , Pereira LE , Butler K , McNicholl SJ , Hendry RM , Kiser PF , Veazey RS , Hope TJ . PLoS Pathog 2016 12 (9) e1005885 Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels. |
Analysis of putative mucosal SHIV susceptibility factors during repeated DMPA treatments in pigtail macaques
Butler K , Ritter J , Ellis S , Henning TR , Montague J , Zaki S , Garber D , McNicholl JM , Kersh EN . J Med Primatol 2015 44 (5) 286-95 BACKGROUND: Depot-medroxyprogesterone acetate (DMPA) has been associated in some studies with increased HIV susceptibility in women. We used a pigtail macaque model to document the effects of repeated DMPA treatments and their potential contribution to increased SHIV susceptibility. METHODS: Nine pigtails were administered 2.5, 1.5, or 0.5 mg/kg DMPA in study weeks one and four. Menstrual cycling, vaginal epithelial thickness, and other SHIV susceptibility factors were monitored for a mean of 24 study weeks. RESULTS: All DMPA treatments suppressed menstrual cycling and increased vaginal pH. The vaginal epithelium thinned naturally during baseline menstrual cycles (from mean of 351 to 161 mum in late-luteal phase). Following DMPA, the non-nucleated layer was temporarily absent. Two weeks post-second DMPA injection, mean epithelial thickness was 53, 45, and 167 mum for the descending doses, respectively. CONCLUSIONS: All animals showed temporal vaginal epithelial thinning with loss of the non-nucleated layer, and vaginal pH changes post-DMPA injections. |
Macaque models of enhanced susceptibility to HIV
Henning TR , McNicholl JM , Vishwanathan SA , Kersh EN . Virol J 2015 12 (1) 90 There are few nonhuman primate models of enhanced HIV susceptibility. Such models can improve comprehension of HIV acquisition risk factors and provide rigorous testing platforms for preclinical prevention strategies. This paper reviews past, current, and proposed research on macaque HIV acquisition risk models and identifies areas where modeling is significantly lacking. We compare different experimental approaches and provide practical considerations for designing macaque susceptibility studies. Modifiable (mucosal and systemic coinfections, hormonal contraception, and rectal lubricants) and non-modifiable (hormonal fluctuations) risk factors are highlighted. Risk acquisition models via vaginal, rectal, and penile challenge routes are discussed. There is no consensus on the best statistical model for evaluating increased susceptibility, and additional research is required. The use of enhanced susceptibility macaque models would benefit multiple facets of the HIV research field, including basic acquisition and pathogenesis studies as well as the vaccine and other biomedical preventions pipeline. |
Viremic control is independent of repeated low-dose SHIV exposures
Henning TR , Hanson D , Vishwanathan SA , Butler K , Dobard C , Garcia-Lerma G , Radzio J , Smith J , McNicholl JM , Kersh EN . AIDS Res Hum Retroviruses 2014 30 (11) 1125-9 The repeat low-dose virus challenge model is commonly used in nonhuman primate studies of HIV transmission and biomedical preventions. For some viruses or challenge routes, it is uncertain whether the repeated exposure design might induce virus-directed innate or adaptive immunity that could affect infection or viremic outcomes. Retrospective cohorts of male Indian rhesus (n=40) and female pigtail (n=46) macaques enrolled in repeat low-dose rectal or vaginal SHIVSF162p3 challenge studies, respectively, were studied to compare the relationship between the number of previous exposures and peak plasma SHIV RNA levels or viral load area under the curve (AUC), surrogate markers of viral control. Repeated mucosal exposures of 10 or 50 TCID50 of virus for rectal and vaginal exposures, respectively, were performed. Virus levels were measured by quantitative reverse-transcriptase real-time PCR. The cumulative number of SHIVSF162p3 exposures did not correlate with observed peak virus levels or with AUC in rectally challenged rhesus macaques [peak: rho (rho)=0.04, p=0.8; AUC: rho=0.33, p=0.06] or vaginally challenged pigtail macaques (peak: rho=-0.09, p=0.7; AUC: rho=0.11, p=0.6). Infections in these models occur independently of exposure history and provide assurance that neither inoculation route nor number of exposures required for infection correlates with postinfection viremia. These data also indicate that both the vaginal and rectal repeated low-dose virus exposure models using SHIVSF162p3 provide a reliable system for nonhuman primate studies. |
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