Correction: Tracking the Luminal Exposure and Lymphatic Drainage Pathways of Intravaginal and Intrarectal Inocula Used in Nonhuman Primate Models of HIV Transmission.

[This corrects the article DOI: 10.1371/journal.pone.0092830.].

Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection.

Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis.

Whole prostate volume and shape changes with the use of an inflatable and flexible endorectal coil.

Purpose. To determine to what extent an inflatable endorectal coil (ERC) affects whole prostate (WP) volume and shape during prostate MRI. Materials and Methods. 79 consecutive patients underwent T2W MRI at 3T first with a 6-channel surface coil and then with the combination of a 16-channel surface coil and ERC in the same imaging session. WP volume was assessed by manually contouring the prostate in each T2W axial slice. PSA density was also calculated. The maximum anterior-posterior (AP), left-right (LR), and craniocaudal (CC) prostate dimensions were measured. Changes in WP prostate volume, PSA density, and prostate dimensions were then evaluated. Results. In 79 patients, use of an ERC yielded no significant change in whole prostate volume (0.6 ± 5.7%, P = 0.270) and PSA density (-0.2 ± 5.6%, P = 0.768). However, use of an ERC significantly decreased the AP dimension of the prostate by -8.6 ± 7.8% (P < 0.001), increased LR dimension by 4.5 ± 5.8% (P < 0.001), and increased the CC dimension by 8.8 ± 6.9% (P < 0.001). Conclusion. Use of an ERC in prostate MRI results in the shape deformation of the prostate gland with no significant change in the volume of the prostate measured on T2W MRI. Therefore, WP volumes calculated on ERC MRI can be reliably used in clinical workflow.

Simultaneous ECG-gated PET imaging of multiple mice.

INTRODUCTION: We describe and illustrate a method for creating ECG-gated PET images of the heart for each of several mice imaged at the same time. The method is intended to increase "throughput" in PET research studies of cardiac dynamics or to obtain information derived from such studies, e.g. tracer concentration in end-diastolic left ventricular blood. METHODS: An imaging bed with provisions for warming, anesthetic delivery, etc., was fabricated by 3D printing to allow simultaneous PET imaging of two side-by-side mice. After electrode attachment, tracer injection and placement of the animals in the scanner field of view, ECG signals from each animal were continuously analyzed and independent trigger markers generated whenever an R-wave was detected in each signal. PET image data were acquired in "list" mode and these trigger markers were inserted into this list along with the image data. Since each mouse is in a different spatial location in the FOV, sorting of these data using trigger markers first from one animal and then the other yields two independent and correctly formed ECG-gated image sequences that reflect the dynamical properties of the heart during an "average" cardiac cycle. RESULTS: The described method yields two independent ECG-gated image sequences that exhibit the expected properties in each animal, e.g. variation of the ventricular cavity volumes from maximum to minimum and back during the cardiac cycle in the processed animal with little or no variation in these volumes during the cardiac cycle in the unprocessed animal. CONCLUSION: ECG-gated image sequences for each of several animals can be created from a single list mode data collection using the described method. In principle, this method can be extended to more than two mice (or other animals) and to other forms of physiological gating, e.g. respiratory gating, when several subjects are imaged at the same time.

Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission.

Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.

Optical imaging of HPV infection in a murine model.

The development of animal models of HPV infection has given investigators a new set of tools to expand basic knowledge of the early events of infection in vivo. The use of HPV pseudovirions, in which the viral genome has been replaced with a reporter pseudogenome, in combination with advanced imaging techniques has facilitated and simplified studies using these models. Herein we provide details for a murine model of cervicovaginal HPV infection in conjunction with several methods for imaging and quantitating the transduced genes, both ex vivo and in vivo.

Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.

The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.