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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


There is currently a great effort world-wide to develop interventions such as vaccines and microbicides to decrease, or hopefully block, HIV transmission. To model the infection of women, the field utilizes the rhesus macaque vaginal transmission model. Understanding the initial events leading to infection after viral challenge of the female reproductive tract (FRT) is crucial for the development of functional prevention strategies. To this end, we developed a novel method for detecting infection in the rhesus macaque FRT after vaginal inoculation. This method utilizes single round replication defective vector that expresses dual reporter proteins, Luciferase and mCherry. Monitoring Luciferase expression allows us to identify the sites of infection within the intact FRT, while fluorescent protein mCherry allows us to visualize the single infected cells. Our studies revealed that virus can access the entire upper and lower reproductive tract. Infection occurs primarily in vaginal and ectocervical tissue, but can spread as far as the ovary and local draining lymph nodes. All classically defined susceptible cell types can be infected with the broadly tropic HIV envelope utilized in this study. Prevention strategies aimed at protecting from HIV infection should consider the entire FRT architecture as potentially susceptible and design interventions accordingly.


Vyšlo v časopise: Vaginal Challenge with an SIV-Based Dual Reporter System Reveals That Infection Can Occur throughout the Upper and Lower Female Reproductive Tract. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004440
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004440

Souhrn

There is currently a great effort world-wide to develop interventions such as vaccines and microbicides to decrease, or hopefully block, HIV transmission. To model the infection of women, the field utilizes the rhesus macaque vaginal transmission model. Understanding the initial events leading to infection after viral challenge of the female reproductive tract (FRT) is crucial for the development of functional prevention strategies. To this end, we developed a novel method for detecting infection in the rhesus macaque FRT after vaginal inoculation. This method utilizes single round replication defective vector that expresses dual reporter proteins, Luciferase and mCherry. Monitoring Luciferase expression allows us to identify the sites of infection within the intact FRT, while fluorescent protein mCherry allows us to visualize the single infected cells. Our studies revealed that virus can access the entire upper and lower reproductive tract. Infection occurs primarily in vaginal and ectocervical tissue, but can spread as far as the ovary and local draining lymph nodes. All classically defined susceptible cell types can be infected with the broadly tropic HIV envelope utilized in this study. Prevention strategies aimed at protecting from HIV infection should consider the entire FRT architecture as potentially susceptible and design interventions accordingly.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


2014 Číslo 10
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