Shehu-Xhilaga Miranda, Kent Stephen, Batten Jane, Ellis Sarah, Van der Meulen Joel, O'Bryan Moira, Cameron Paul U, Lewin Sharon R, Hedger Mark P
Infectious Diseases Unit, Alfred Hospital, Prahran, Australia.
Retrovirology. 2007 Jan 31;4:7. doi: 10.1186/1742-4690-4-7.
Little is known about the progression and pathogenesis of HIV-1 infection within the male genital tract (MGT), particularly during the early stages of infection.
To 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, alphabetaTCR. Infection of spermatogonia, but not more mature spermatogenic cells, was also observed. Leukocytic infiltrates were observed within the epididymal stroma of the infected animals.
These 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.
关于人类免疫缺陷病毒1型（HIV-1）在男性生殖道（MGT）内的进展和发病机制，人们了解甚少，尤其是在感染的早期阶段。
为了研究睾丸和附睾中的HIV发病机制，12只幼年猕猴（食蟹猴，4 - 4.5岁）感染了猴免疫缺陷病毒mac 251（SIVmac251）（n = 6）或猴/人免疫缺陷病毒（SHIVmn229）（n = 6）。在感染后的第11 - 13周（SHIV）和第23周（SIV）收集睾丸和附睾，并通过光学显微镜和电子显微镜进行检查。发现猕猴MGT的成熟状态存在差异，从青春期前（缺乏减数分裂后生殖细胞）到青春期后（附睾管中有成熟精子）。在用SHIVmn229和SIVmac251感染后，在淋巴结、附睾和睾丸中鉴定出了不同水平的病毒RNA。通过使用针对SIV（抗gp41）和HIV-1（衣壳/p24）蛋白的特异性抗体进行免疫荧光组织化学检测病毒蛋白。通过使用针对CD68、DC-SIGN、αβTCR的抗体进行共定位研究，确定SIV和SHIV感染了睾丸间质组织中的巨噬细胞、可能的树突状细胞和T细胞。还观察到精原细胞受到感染，但更成熟的生精细胞未受感染。在受感染动物的附睾基质中观察到白细胞浸润。
这些数据表明，幼年猕猴的睾丸和附睾是感染后急性期SIV和SHIV的靶器官，代表了研究HIV-1发病机制及其对精子发生和一般MGT影响的潜在模型。
