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Infection of semen-producing organs by SIV during the acute and chronic stages of the disease.

Le Tortorec A, Le Grand R, Denis H, Satie AP, Mannioui K, Roques P, Maillard A, Daniels S, Jégou B, Dejucq-Rainsford N - PLoS ONE (2008)

Bottom Line: We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation.The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes.Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA.

View Article: PubMed Central - PubMed

Affiliation: INSERM U625, Rennes, University of Rennes I, Groupe d'Etude de la Reproduction chez l'Homme et les Mammifères, IFR 140, Campus de Beaulieu, Rennes, France.

ABSTRACT

Background: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals.

Methodology/principal findings: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected.

Conclusions/significance: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen.

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Related in: MedlinePlus

SIV DNA detection and quantification in the male genital organs.(A) Frequency of detection of SIV DNA in the testis, epididymis (Epid.), prostate and seminal vesicle (Sem. Ves.) of SIV-infected macaques, using nested SIV gag PCR. Each bar represents the mean +/− SEM of gag+ PCR for each organ within a group of animals. Statistical difference (Kruskal Wallis test, p<0.05) was found between the MGT of primary-infected, high chronic and low chronic animals (not shown on the graph); p values shown on the graph indicate statistical difference between the organs, according to Wilcoxon signed rank test. (B) Frequencies of detection of SIV gag DNA in genital organs of primary and chronically-infected animals were tested for association with blood viremia by Spearman rank test. The different organs are depicted by different symbols. Positive correlation was found for all male genital tract organs levels of infection and blood viral load. (C) SIV DNA viral load in mesenteric lymph nodes (LN), epididymides, prostate and seminal vesicles of primary SIV-infected macaques, in quantitative real time PCR. Mean of 4 animals is represented by black bars. Squares with the same pattern show viral load for 2 independent fragments of the same organ. Stars indicate statistical difference between the epididymis and the other organs (Wilcoxon signed rank test, p<0.05).
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pone-0001792-g003: SIV DNA detection and quantification in the male genital organs.(A) Frequency of detection of SIV DNA in the testis, epididymis (Epid.), prostate and seminal vesicle (Sem. Ves.) of SIV-infected macaques, using nested SIV gag PCR. Each bar represents the mean +/− SEM of gag+ PCR for each organ within a group of animals. Statistical difference (Kruskal Wallis test, p<0.05) was found between the MGT of primary-infected, high chronic and low chronic animals (not shown on the graph); p values shown on the graph indicate statistical difference between the organs, according to Wilcoxon signed rank test. (B) Frequencies of detection of SIV gag DNA in genital organs of primary and chronically-infected animals were tested for association with blood viremia by Spearman rank test. The different organs are depicted by different symbols. Positive correlation was found for all male genital tract organs levels of infection and blood viral load. (C) SIV DNA viral load in mesenteric lymph nodes (LN), epididymides, prostate and seminal vesicles of primary SIV-infected macaques, in quantitative real time PCR. Mean of 4 animals is represented by black bars. Squares with the same pattern show viral load for 2 independent fragments of the same organ. Stars indicate statistical difference between the epididymis and the other organs (Wilcoxon signed rank test, p<0.05).

Mentions: Nested PCR detected SIV-DNA in the testis, epididymis and accessory glands of all acutely-infected animals (Figure 3A). During this phase, SIV detection rate in the MGT was significantly higher than during chronic phase. Furthermore, MGT infection was significantly reduced in low chronic animals when compared to high chronics (Figure 3A). A positive correlation was found between the frequency of detection of SIV in the MGT and blood viremia (Figure 3B). Throughout the infection, the testis displayed the lowest rate of infection amongst the organs tested, a finding confirmed in primary-infected animals by measurement of reproductive tissues viral load (VL) in real time PCR: prostate and seminal vesicles VL were on average 1 Log higher than epididymis mean VL (Figure 3C), whilst testis VL was consistently below the quantification threshold of the real time PCR. Of note, semen-producing organs VLs were at least 1 Log lower than mesenteric lymph node VL.


Infection of semen-producing organs by SIV during the acute and chronic stages of the disease.

Le Tortorec A, Le Grand R, Denis H, Satie AP, Mannioui K, Roques P, Maillard A, Daniels S, Jégou B, Dejucq-Rainsford N - PLoS ONE (2008)

SIV DNA detection and quantification in the male genital organs.(A) Frequency of detection of SIV DNA in the testis, epididymis (Epid.), prostate and seminal vesicle (Sem. Ves.) of SIV-infected macaques, using nested SIV gag PCR. Each bar represents the mean +/− SEM of gag+ PCR for each organ within a group of animals. Statistical difference (Kruskal Wallis test, p<0.05) was found between the MGT of primary-infected, high chronic and low chronic animals (not shown on the graph); p values shown on the graph indicate statistical difference between the organs, according to Wilcoxon signed rank test. (B) Frequencies of detection of SIV gag DNA in genital organs of primary and chronically-infected animals were tested for association with blood viremia by Spearman rank test. The different organs are depicted by different symbols. Positive correlation was found for all male genital tract organs levels of infection and blood viral load. (C) SIV DNA viral load in mesenteric lymph nodes (LN), epididymides, prostate and seminal vesicles of primary SIV-infected macaques, in quantitative real time PCR. Mean of 4 animals is represented by black bars. Squares with the same pattern show viral load for 2 independent fragments of the same organ. Stars indicate statistical difference between the epididymis and the other organs (Wilcoxon signed rank test, p<0.05).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2268241&req=5

pone-0001792-g003: SIV DNA detection and quantification in the male genital organs.(A) Frequency of detection of SIV DNA in the testis, epididymis (Epid.), prostate and seminal vesicle (Sem. Ves.) of SIV-infected macaques, using nested SIV gag PCR. Each bar represents the mean +/− SEM of gag+ PCR for each organ within a group of animals. Statistical difference (Kruskal Wallis test, p<0.05) was found between the MGT of primary-infected, high chronic and low chronic animals (not shown on the graph); p values shown on the graph indicate statistical difference between the organs, according to Wilcoxon signed rank test. (B) Frequencies of detection of SIV gag DNA in genital organs of primary and chronically-infected animals were tested for association with blood viremia by Spearman rank test. The different organs are depicted by different symbols. Positive correlation was found for all male genital tract organs levels of infection and blood viral load. (C) SIV DNA viral load in mesenteric lymph nodes (LN), epididymides, prostate and seminal vesicles of primary SIV-infected macaques, in quantitative real time PCR. Mean of 4 animals is represented by black bars. Squares with the same pattern show viral load for 2 independent fragments of the same organ. Stars indicate statistical difference between the epididymis and the other organs (Wilcoxon signed rank test, p<0.05).
Mentions: Nested PCR detected SIV-DNA in the testis, epididymis and accessory glands of all acutely-infected animals (Figure 3A). During this phase, SIV detection rate in the MGT was significantly higher than during chronic phase. Furthermore, MGT infection was significantly reduced in low chronic animals when compared to high chronics (Figure 3A). A positive correlation was found between the frequency of detection of SIV in the MGT and blood viremia (Figure 3B). Throughout the infection, the testis displayed the lowest rate of infection amongst the organs tested, a finding confirmed in primary-infected animals by measurement of reproductive tissues viral load (VL) in real time PCR: prostate and seminal vesicles VL were on average 1 Log higher than epididymis mean VL (Figure 3C), whilst testis VL was consistently below the quantification threshold of the real time PCR. Of note, semen-producing organs VLs were at least 1 Log lower than mesenteric lymph node VL.

Bottom Line: We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation.The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes.Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA.

View Article: PubMed Central - PubMed

Affiliation: INSERM U625, Rennes, University of Rennes I, Groupe d'Etude de la Reproduction chez l'Homme et les Mammifères, IFR 140, Campus de Beaulieu, Rennes, France.

ABSTRACT

Background: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals.

Methodology/principal findings: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected.

Conclusions/significance: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen.

Show MeSH
Related in: MedlinePlus