Abstract
BackgroundAPOBEC3 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).ResultsWe 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.ConclusionOur data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.
Highlights
APOBEC3 proteins are host factors that restrict infection by retroviruses like human immunodeficiency virus (HIV), MMTV, and murine leukemia viruses (MLV) and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells
Results mouse A3 (mA3) is expressed in genital tract tissues and gametes Healthy female and male C57BL/6 mice were euthanized, and different genital tract tissues and gametes were obtained for analysis of mA3 mRNA levels by realtime quantitative PCR
MA3-deficient mice have increased susceptibility to acute LP-BM5 infection Since male genital organs and gametes express mA3, and since we previously showed that mA3 deficient mice are more susceptible to MLV and MMTV [45,46,51,52], we hypothesize that mice lacking the mA3 gene will have higher virus load upon infection with LP-BM5
Summary
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. 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). Viruses that use the genital mucosa as a portal of entry into the host include HPV, HSV, hepatitis B virus, and retroviruses like SIV, MLV, and HIV. We utilize the murine acquired immunodeficiency syndrome (mAIDs) model
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