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Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

ABSTRACT: The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.

SUBMITTER: Stieh DJ

PROVIDER: S-EPMC4192600 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

Stieh Daniel J DJ Maric Danijela D Kelley Z L ZL Anderson Meegan R MR Hattaway Holly Z HZ Beilfuss Beth A BA Rothwangl Katharina B KB Veazey Ronald S RS Hope Thomas J TJ

PLoS pathogens 20141009 10

The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum usi ...[more]

PMID: 25299616

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Project description:Recurrent spontaneous abortion (RSA) is a complex multifactorial disease. Recently, the microbiota of the female reproductive tract, as an emerging factor in RSA, has gradually attracted the attention of many clinical researchers. Here, we reported that the microbiota of the lower and upper female reproductive tracts from patients with RSA showed no significant differences in alpha diversity compared to that of controls. Beta diversity was significantly higher in the RSA group than in the control group in the vaginal microbiota (P = 0.036), cervical microbiota (P = 0.010) and microbiota from uterine lavage fluid (P = 0.001). In addition, dramatic decreases in gamma interferon and interleukin-6 cytokine levels were observed in the RSA group. In conclusion, our data suggested altered microbial biodiversity in the vagina, cervix and uterine lavage fluid in the RSA group. Alterations in the microbiota in the uterine cavity could be associated with altered cytokine levels, which might be a risk factor for RSA pathogenesis. Moreover, the microbiota composition differed markedly from the lower genital tract to the uterine cavity, and the microbiota in the uterine cavity also distinctly varied between endometrial tissue and uterine lavage fluid in the RSA group. Hence, sampling with these two methods simultaneously allowed a more comprehensive perspective of microbial colonization in the uterine cavity. IMPORTANCE As an obstacle to pregnancy, recurrent spontaneous abortion (RSA) can be caused by a variety of factors, and a current understanding of the etiology of RSA is still lacking; half of cases have an unknown cause. A substantial fraction of patients show no improvement after treatment. Since the microbiota of the female reproductive tract has been proposed as an emerging factor in RSA patients, further investigation is needed to provide guidance for clinical therapy. In general, this is the first report describing the distinct alterations of the vaginal, cervical, and uterine microbiota in RSA, not just that in the vagina. Furthermore, another major strength of this study derived from the further in-depth investigation and analysis of the characteristics of the microbiota colonizing the upper female genital tract in RSA, which provided a more comprehensive view for investigating the uterine microbiota.

Project description:BackgroundUnderstanding the complex structures and interactions of the bacterial communities inhabiting the upper (URT) and lower (LRT) respiratory tract of pigs is at an early stage. The objective of this study was to characterize the bacterial topography of three URT (nostrils, choana, and tonsils) and LRT (proximal trachea, left caudal lobe and secondary bronchi) sites in pigs. Thirty-six post-mortem samples from six pigs were analysed by 16S rRNA gene quantification and sequencing, and the microbiota in nostrils and trachea was additionally profiled by shotgun sequencing.ResultsThe bacterial composition obtained by the two methods was congruent, although metagenomics recovered only a fraction of the diversity (32 metagenome-assembled genomes) due to the high proportion (85-98%) of host DNA. The highest abundance of 16S rRNA copies was observed in nostrils, followed by tonsils, trachea, bronchi, choana and lung. Bacterial richness and diversity were lower in the LRT compared to the URT. Overall, Firmicutes and Proteobacteria were identified as predominant taxa in all sample types. Glasserella (15.7%), Streptococcus (14.6%) and Clostridium (10.1%) were the most abundant genera but differences in microbiota composition were observed between the two tracts as well as between sampling sites within the same tract. Clear-cut differences were observed between nasal and tonsillar microbiomes (R-values 0.85-0.93), whereas bacterial communities inhabiting trachea and lung were similar (R-values 0.10-0.17). Moraxella and Streptococcus were more common in bronchial mucosal scraping than in lavage, probably because of mucosal adherence. The bacterial microbiota of the choana was less diverse than that of the nostrils and similar to the tracheal microbiota (R-value 0.24), suggesting that the posterior nasal cavity serves as the primary source of bacteria for the LRT.ConclusionWe provide new knowledge on microbiota composition and species abundance in distinct ecological niches of the pig respiratory tract. Our results shed light on the distribution of opportunistic bacterial pathogens across the respiratory tract and support the hypothesis that bacteria present in the lungs originate from the posterior nasal cavity. Due to the high abundance of host DNA, high-resolution profiling of the pig respiratory microbiota by shotgun sequencing requires methods for host DNA depletion.

Dataset Information

Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

Publications

Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.

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