HIV-1 nucleic acids localize to the spermatogonia and their progeny. A study by polymerase chain reaction in-situ hybridization. Am. J. Pathol. 144, 1142-8

Department of Pathology, SUNY at Stony Brook 11794-8691.
American Journal Of Pathology (Impact Factor: 4.59). 07/1994; 144(6):1142-8.
Source: PubMed


The purpose of this study was to determine the histological distribution of in situ polymerase chain reaction (PCR)-amplified HIV-1 nucleic acids in the male genital tract to elucidate the mechanism of sexual transmission of AIDS. Viral DNA was detected in the testicular tissue of 11 of 12 men with HIV-1 infection using the PCR in situ hybridization technique. The amplified viral DNA localized to many spermatogonia, spermatocytes, and rare spermatids. Relatively few viral infected macrophages were noted, mostly in the prostate. The viral infection was activated given the presence of cDNA sequences consistent with genomic and multiple spliced transcripts as determined by reverse transcription in situ PCR. PCR-amplified viral nucleic acids were not detected in the epithelial of the prostate, epididymis, seminal vesicles, or penis in men with AIDS nor in any genital tract tissues from three boys who died of AIDS acquired in utero. The demonstration that HIV-1 selectively infects the spermatogonia and their progeny suggests that this may serve as a primary source of venereal spread of the virus. Concomitant destruction of these cells by HIV-1 may also explain the marked inhibition of spermatogenesis and severe atrophy that characterizes the testes in AIDS.

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Available from: Jürgen C Becker, Mar 06, 2015
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    • "Indeed, we show that seminal fluid of APOBEC3 knock mice harbors more LP-BM5 virus compared to the wild type as visualized by Western blot (Figure 4G), but we were unable to detect APOBEC3 due to perhaps the lack of good anti-mouse APOBEC3 antibodies or limited viral protein in samples from APOBEC3 sufficient mice. The detection of LP-BM5 proviral DNA in spermatozoa and testes support previous observations made with HIV-1 and herpesvirus type 8 [77-80]. "
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    ABSTRACT: 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.
    Full-text · Article · Jun 2012 · Retrovirology
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    • "It remains unclear how lentiviral particles attach or are absorbed on sperm surface, or if they are internalized into the sperm cell and integrated in the genome. In fact, it has been reported that HIV-1 was detected in human spermatozoa by PCR [30], and HIV-1 may be harbored on the human sperm tail [31]. However, the peudotyped lentivirus utilized in our study contains a VSV-G envelope, and it is not clear how these surface proteins interact with the pig spermatozoa. "
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    ABSTRACT: Sperm-mediated gene transfer can be a very efficient method to produce transgenic pigs, however, the results from different laboratories had not been widely repeated. Genomic integration of transgene by injection of pseudotyped lentivirus to the perivitelline space has been proved to be a reliable route to generate transgenic animals. To test whether transgene in the lentivirus can be delivered by sperm, we studied incubation of pseudotyped lentiviruses and sperm before insemination. After incubation with pig spermatozoa, 62±3 lentiviral particles were detected per 100 sperm cells using quantitative real-time RT-PCR. The association of lentivirus with sperm was further confirmed by electron microscopy. The sperm incubated with lentiviral particles were artificially inseminated into pigs. Of the 59 piglets born from inseminated 5 sows, 6 piglets (10.17%) carried the transgene based on the PCR identification. Foreign gene and EGFP was successfully detected in ear tissue biopsies from two PCR-positive pigs, revealed via in situ hybridization and immunohistochemistry. Offspring of one PCR-positive boar with normal sows showed PCR-positive. Two PCR-positive founders and offsprings of PCR-positive boar were further identified by Southern-blot analysis, out of which the two founders and two offsprings were positive in Southern blotting, strongly indicating integration of foreign gene into genome. The results indicate that incubation of sperm with pseudotyped lentiviruses can incorporated with sperm-mediated gene transfer to produce transgenic pigs with improved efficiency.
    Preview · Article · Apr 2012 · PLoS ONE
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    • "This prompts us to go back to the primary question of whether the spermatozoa in male HIV/AIDS patients carry HIV-1. Despite the initial long debate, the presence of viral particles and nucleic acids in spermatozoa from HIV-1-infected men was finally confirmed using a variety of techniques [4]–[9]. Horizontal transmission and vertical transmission of HIV by spermatozoa have been demonstrated by two separate research groups, and both indicated that the virus is transmitted through cell-to-cell contact [3], [10]. "
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    ABSTRACT: Complete understanding of the route of HIV-1 transmission is an important prerequisite for curbing the HIV/AIDS pandemic. So far, the known routes of HIV-1 transmission include sexual contact, needle sharing, puncture, transfusion and mother-to-child transmission. Whether HIV can be vertically transmitted from human sperm to embryo by fertilization is largely undetermined. Direct research on embryo derived from infected human sperm and healthy human ova have been difficult because of ethical issues and problems in the collection of ova. However, the use of inter-specific in vitro fertilization (IVF) between human sperm and hamster ova can avoid both of these problems. Combined with molecular, cytogenetical and immunological techniques such as the preparation of human sperm chromosomes, fluorescent in situ hybridization (FISH), and immunofluorescence assay (IFA), this study mainly explored whether any integrated HIV provirus were present in the chromosomes of infected patients' sperm, and whether that provirus could be transferred into early embryos by fertilization and maintain its function of replication and expression. Evidence showed that HIV-1 nucleic acid was present in the spermatozoa of HIV/AIDS patients, that HIV-1 provirus is present on the patient sperm chromosome, that the integrated provirus could be transferred into early embryo chromosomally integrated by fertilization, and that it could replicate alongside the embryonic genome and subsequently express its protein in the embryo. These findings indicate the possibility of vertical transmission of HIV-1 from the sperm genome to the embryonic genome by fertilization. This study also offers a platform for the research into this new mode of transmission for other viruses, especially sexually transmitted viruses.
    Full-text · Article · Dec 2011 · PLoS ONE
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