Abstract
BackgroundLittle is known about the progression and pathogenesis of HIV-1 infection within the male genital tract (MGT), particularly during the early stages of infection.ResultsTo study HIV pathogenesis in the testis and epididymis, 12 juvenile monkeys (Macacca nemestrina, 4–4.5 years old) were infected with Simian Immunodeficiency Virus mac 251 (SIVmac251) (n = 6) or Simian/Human Immunodeficiency Virus (SHIVmn229) (n = 6). Testes and epididymides were collected and examined by light microscopy and electron microscopy, at weeks 11–13 (SHIV) and 23 (SIV) following infection. Differences were found in the maturation status of the MGT of the monkeys, ranging from prepubertal (lacking post-meiotic germ cells) to post-pubertal (having mature sperm in the epididymal duct). Variable levels of viral RNA were identified in the lymph node, epididymis and testis following infection with both SHIVmn229 and SIVmac251. Viral protein was detected via immunofluorescence histochemistry using specific antibodies to SIV (anti-gp41) and HIV-1 (capsid/p24) protein. SIV and SHIV infected macrophages, potentially dendritic cells and T cells in the testicular interstitial tissue were identified by co-localisation studies using antibodies to CD68, DC-SIGN, αβTCR. Infection of spermatogonia, but not more mature spermatogenic cells, was also observed. Leukocytic infiltrates were observed within the epididymal stroma of the infected animals.ConclusionThese data show that the testis and epididymis of juvenile macaques are a target for SIV and SHIV during the post-acute stage of infection and represent a potential model for studying HIV-1 pathogenesis and its effect on spermatogenesis and the MGT in general.
Highlights
Little is known about the progression and pathogenesis of HIV-1 infection within the male genital tract (MGT), during the early stages of infection
In the setting of orchitis in HIV-1 infected patients with AIDS, infiltration of tubules by CD4+ T cells has been described [4]. It is unclear whether resident macrophages and CD4+ T cells of the testis are a target for infection in the early stages of HIV-1 infection or whether this is a feature only of the late stages of the disease
It is believed that HIV-1 infected CD4+ T cells, macrophages and spermatogenic cells from the testis and epididymis are shed into the semen during the course of HIV-1 infection [8,5], contributing to viral transmission, though further evidence to support this opinion is needed
Summary
Little is known about the progression and pathogenesis of HIV-1 infection within the male genital tract (MGT), during the early stages of infection. In the setting of orchitis in HIV-1 infected patients with AIDS, infiltration of tubules by CD4+ T cells has been described [4]. It is unclear whether resident macrophages and CD4+ T cells of the testis are a target for infection in the early stages of HIV-1 infection or whether this is a feature only of the late stages of the disease. It is believed that HIV-1 infected CD4+ T cells, macrophages and spermatogenic cells from the testis and epididymis are shed into the semen during the course of HIV-1 infection [8,5], contributing to viral transmission, though further evidence to support this opinion is needed
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