Department of Microbiology, Carver College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242-1109, USA.
Retrovirology. 2012 Jun 12;9:50. doi: 10.1186/1742-4690-9-50.
APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV - the etiological agent of murine AIDs (mAIDs).
We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner.
Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.
APOBEC3 蛋白是宿主因子,可限制 HIV、MMTV 和 MLV 等逆转录病毒的感染,并在造血和非造血细胞(如巨噬细胞、淋巴细胞、树突状细胞和上皮细胞)中差异表达。此前,我们发现乳腺上皮细胞中表达的 APOBEC3 可限制β-逆转录病毒,即鼠乳腺肿瘤病毒的乳源性传播。在本研究中,我们使用 APOBEC3 敲除小鼠及其野生型对照来研究 APOBEC3 在 LP-BM5 MLV 性传播中的作用,LP-BM5 MLV 是鼠获得性免疫缺陷综合征(mAIDs)的病因。
我们表明,鼠 APOBEC3 在鼠生殖道组织和配子中表达,且 APOBEC3 缺陷小鼠的生殖道组织更易被 LP-BM5 病毒感染。生殖道组织中的 APOBEC3 可能在降低通过性途径传播的病毒方面发挥作用,因为缺乏 APOBEC3 基因的小鼠具有更高的生殖道和精液病毒载量,并且与 APOBEC3+小鼠相比,更有效地将病毒通过性途径传播给其伴侣。此外,我们表明,经 LP-BM5 病毒感染的雌性小鼠以 APOBEC3 依赖的方式将病毒传播给后代。
我们的数据表明,固有 APOBEC3 限制生殖道感染并限制 LP-BM5 病毒的性传播。