ABSTRACT
BACKGROUND: 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). RESULTS: 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. CONCLUSION: Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.
Subject(s)
Cytidine Deaminase/metabolism , Genitalia/virology , Leukemia Virus, Murine/pathogenicity , Murine Acquired Immunodeficiency Syndrome/transmission , Sexually Transmitted Diseases, Viral/transmission , Animals , Cytidine Deaminase/genetics , Disease Susceptibility/metabolism , Disease Susceptibility/virology , Female , Genitalia/metabolism , Germ Cells/metabolism , Germ Cells/virology , Leukemia Virus, Murine/metabolism , Male , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/virology , Mice , Mice, Inbred C57BL , Mice, Knockout , Murine Acquired Immunodeficiency Syndrome/metabolism , Murine Acquired Immunodeficiency Syndrome/virology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sexually Transmitted Diseases, Viral/metabolism , Splenomegaly/virology , Viral LoadABSTRACT
Heterosexual transmission of a murine leukemia virus mixture named LP-BM5 MuLV, which is known as the murine AIDS virus, was investigated. Our results indicated that the heterosexual transmission of LP-BM5 MuLV occurs in both directions with high frequency and that the frequencies of virus transmission in the cervix and penis are higher than those in other genital organs. The results suggested that infection by LP-BM5 MuLV via heterosexual transmission may initially take place at particular retrovirus-sensitive sites (cells) in the genital organs.
Subject(s)
Disease Transmission, Infectious , Leukemia Virus, Murine , Murine Acquired Immunodeficiency Syndrome/transmission , Animals , Cell Line , DNA, Viral , Female , Heterosexuality , Leukemia Virus, Murine/genetics , Leukemia Virus, Murine/isolation & purification , Male , Mice , Mice, Inbred C57BL , Murine Acquired Immunodeficiency Syndrome/pathology , Murine Acquired Immunodeficiency Syndrome/virologyABSTRACT
Maternal transmission of a murine leukemia virus (MuLV) mixture named LP-BM5 MuLV, which is knwon to induce murine AIDS (MAIDS), was investigated. Adult female C57BL/10 mice were inoculated intraperitoneally with LP-BM5 MuLV. When the virus-inoculated female mice developed splenomegaly or lymphadenopathy, they were mated with normal C57BL/10 male mice. Of 56 offspring born to MAIDS mothers, 14 appeared to develop MAIDS, as assessed by the occurrence of splenomegaly or lymphadenopathy as well as the mitogen response of spleen cells. The occurrence of MAIDS in offspring was found to be accompanied by the maternal transmission and expansion of a defective virus genome from which almost the entire pol and env regions are deleted. On the other hand, the ecotropic helper virus genome was detected in all offspring regardless of the occurrence of MAIDS. To examine the mode of maternal transmission of LP-BM5 MuLV, foster-nursing experiments were conducted. The ecotropic helper viruses were found in all normal offspring nursed by a MAIDS mother, and some of them developed MAIDS. In contrast, none of offspring born to a MAIDS mother that were nursed by an uninfected foster mother either carried the LP-BM5 MuLV or developed MAIDS. Finally, both the defective and the ecotropic helper viruses were detected in LP-BM5 MuLV-infected mother's milk. These results indicated that maternal transmission of LP-BM5 MuLV occurs with a high frequency and is mediated by mother's milk.
Subject(s)
Defective Viruses/pathogenicity , Leukemia Virus, Murine/pathogenicity , Milk/microbiology , Murine Acquired Immunodeficiency Syndrome/transmission , Animals , Base Sequence , Defective Viruses/isolation & purification , Disease Models, Animal , Female , Genes, env/genetics , Genes, pol/genetics , Genome, Viral , Helper Viruses/isolation & purification , Leukemia Virus, Murine/isolation & purification , Male , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Pregnancy , VirulenceSubject(s)
Murine Acquired Immunodeficiency Syndrome/transmission , Animals , Female , Male , Maternal-Fetal Exchange , Mice , Mice, Inbred C57BL , Pregnancy , RectumABSTRACT
LP-BM5 MuLV infection of monocyte-macrophages (MM cells) and the ability of MM cells infected with this murine oncornavirus complex to transmit murine acquired immune deficiency syndrome (MAIDS) were assessed. Adherent cells expressing Mac-1 antigen (Mac-1+) were isolated from the peritoneum of infected C57BL/6 mice at weekly intervals postinoculation. A small percentage of MM cells was infected by 7 days after inoculation with LP-BM5 MuLV and virus production could be detected in MM cells throughout the course of disease. MAIDS could be induced in naive C57BL/6 mice by i.p. injection of 0.5-3 x 10(5) MM cells derived from infected mice as early as 8 weeks postinfection. When 3 x 10(5) cells (300 infectious centers) were injected, the progression of disease was similar to that seen after inoculation with a known virus pool (log10 5.78 XC pfu/ml). Treatment with zidovudine (ZDV) at 1 mg/ml in drinking water delayed disease progression if started 24 h prior to inoculation of MM cells and given continuously.
