Limits...
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.

Show MeSH

Related in: MedlinePlus

Immune activation in the male genital organs.Immunohistochemical detection of HLA-DR+ cells in the prostate (A–C), seminal vesicle (D–F), epididymis (G–I) and testis (J–L) of uninfected (A, D, G, J), primary-infected (B, E, H, K) or high chronic macaques (C, F, I, L). Scale bars = 100 µm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2268241&req=5

pone-0001792-g006: Immune activation in the male genital organs.Immunohistochemical detection of HLA-DR+ cells in the prostate (A–C), seminal vesicle (D–F), epididymis (G–I) and testis (J–L) of uninfected (A, D, G, J), primary-infected (B, E, H, K) or high chronic macaques (C, F, I, L). Scale bars = 100 µm.

Mentions: The morphology of the seminal vesicles, epididymides and testes was similar in acutely-infected animals (Figure 6E, H, K) when compared to uninfected ones (Figure 6D, G, J). However, HLA-DR+ cell foci were observed within the prostate during the acute phase of the infection (Figure 6B versus Figure 6A). In low chronic animals, cell foci were never observed (data not shown). In contrast, in high chronic animals, outsized HLA-DR+ cell infiltrates were observed in the stroma of the prostate (Figure 6C), seminal vesicles (Figure 6F) and epididymides (Figure 6I), but were never found within the testis (Figure 6L). During both the primary and chronic stage of the disease, the cellular infiltrates were mainly composed of CD3+ T lymphocytes and comprised a mix of CD4+ T helper and TIA-1+ cytotoxic cells (Figure 7E, F, G and M, N, O) whilst only very few cells labelled with the NK marker Pen5 (Figure 7H and P); only a few CD20+ B lymphocytes (Figure 7C and K) and CD68+ myeloid cells (Figure 7B and J) were present. Semi-quantitative analysis indicated that there were no marked differences between the sizes and number of CD3+ T cell foci amongst the epididymis and accessory glands of chronically-infected macaques with high PVL. Although the prostate of primary-infected animals displayed similar numbers of small size CD3+ infiltrates (15–50 cells) than the prostate of high chronic macaques, medium size foci (51–250 cells) were 2.7 fold less numerous and large size foci (251–1000 cells) were never encountered (Figure 7Q).


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)

Immune activation in the male genital organs.Immunohistochemical detection of HLA-DR+ cells in the prostate (A–C), seminal vesicle (D–F), epididymis (G–I) and testis (J–L) of uninfected (A, D, G, J), primary-infected (B, E, H, K) or high chronic macaques (C, F, I, L). Scale bars = 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2268241&req=5

pone-0001792-g006: Immune activation in the male genital organs.Immunohistochemical detection of HLA-DR+ cells in the prostate (A–C), seminal vesicle (D–F), epididymis (G–I) and testis (J–L) of uninfected (A, D, G, J), primary-infected (B, E, H, K) or high chronic macaques (C, F, I, L). Scale bars = 100 µm.
Mentions: The morphology of the seminal vesicles, epididymides and testes was similar in acutely-infected animals (Figure 6E, H, K) when compared to uninfected ones (Figure 6D, G, J). However, HLA-DR+ cell foci were observed within the prostate during the acute phase of the infection (Figure 6B versus Figure 6A). In low chronic animals, cell foci were never observed (data not shown). In contrast, in high chronic animals, outsized HLA-DR+ cell infiltrates were observed in the stroma of the prostate (Figure 6C), seminal vesicles (Figure 6F) and epididymides (Figure 6I), but were never found within the testis (Figure 6L). During both the primary and chronic stage of the disease, the cellular infiltrates were mainly composed of CD3+ T lymphocytes and comprised a mix of CD4+ T helper and TIA-1+ cytotoxic cells (Figure 7E, F, G and M, N, O) whilst only very few cells labelled with the NK marker Pen5 (Figure 7H and P); only a few CD20+ B lymphocytes (Figure 7C and K) and CD68+ myeloid cells (Figure 7B and J) were present. Semi-quantitative analysis indicated that there were no marked differences between the sizes and number of CD3+ T cell foci amongst the epididymis and accessory glands of chronically-infected macaques with high PVL. Although the prostate of primary-infected animals displayed similar numbers of small size CD3+ infiltrates (15–50 cells) than the prostate of high chronic macaques, medium size foci (51–250 cells) were 2.7 fold less numerous and large size foci (251–1000 cells) were never encountered (Figure 7Q).

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