Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Sci Adv. 2017 Feb 22;3(2):e1602899. doi: 10.1126/sciadv.1602899. eCollection 2017 Feb.
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males.
Zika 病毒（ZIKV）是一种新兴的蚊媒黄病毒，最近被发现可导致胎儿感染和新生儿异常，包括小头畸形和神经功能障碍。ZIKV 在人类急性病毒血症期过后数月仍存在于精液中。为了进一步了解 ZIKV 在男性体内持续存在的后果，我们通过皮下注射一种具有致病性但非致死性的 ZIKV 株感染小鼠。即使在血液中清除后，ZIKV 仍在睾丸内复制，间质中产生睾酮的莱迪希细胞支持病毒复制。我们在储存精子的附睾管腔以及周围的上皮细胞中发现了高水平的病毒 RNA 和抗原。出乎意料的是，在感染后 21 天，与 mock 感染组相比，ZIKV 感染组的小鼠睾丸明显变小，表明睾丸进行性萎缩。ZIKV 感染导致血清睾酮水平降低，提示男性生育能力可能受到影响。我们的研究结果对于非媒介传播的垂直传播以及 ZIKV 感染男性的长期潜在生殖缺陷具有重要意义。
