Localization of infection in neonatal rhesus macaques after oral viral challenge
Localization of infection in neonatal rhesus macaques after oral viral challenge
Abstract While vertical transmission of human immunodeficiency virus (HIV) can occur in utero and during delivery and through breastfeeding. We utilized Positron Emission Tomography (PET) imaging coupled with fluorescent microscopy of 64Cu-labeled photoactivatable-GFP-HIV (PA-GFP-BaL) to determine how HIV virions distribute and localize in neonatal rhesus macaques two and four hours after oral viral challenge. Our results show that by four hours after oral viral exposure, HIV virions localize to and penetrate the rectal mucosa. We also used a dual viral challenge with a non-replicative viral vector and a replication competent SHIV-1157ipd3N4 to examine viral transduction and dissemination at 96 hours. Our data show that while SHIV-1157ipd3N4 infection can be found in the oral cavity and upper gastrointestinal (GI) tract, the small and large intestine contained the largest number of infected cells. Moreover, we found that T cells were the biggest population of infected immune cells. Thus, thanks to these novel technologies, we are able to visualize and delineate of viral distribution and infection throughout the entire neonatal GI tract during acute viral infection. Author SummaryApproximately 1.8 million children are currently living with human immunodeficiency virus (HIV). While mother-to-child HIV transmission can occur in utero and during delivery, it most commonly occurs through breastfeeding, creating the need to understand how the virus moves throughout the body and infects the infant once breast milk is consumed. Here, we used multiple imaging techniques and PCR to determine how HIV distributes throughout the gastrointestinal tract after oral viral exposure and in which tissues and cell types become acutely infected. We found that HIV rapidly spreads throughout and penetrates the entire gastrointestinal tract as early as four hours after exposure. We also found that the intestine contained the largest number of infected cells at 96 hours and that most cells infected were T cells. Our study shows that these imaging technologies allow for the examination of viral distribution and infection in a rhesus macaque model.
Allen Edward J.、Lorenzo-Redondo Ramon、Carias Ann M.、Anderson Meegan R.、Villinger Francois J、Lakhashe Samir、Ara¨anga Mariluz、Ruprecht Ruth M.、Strickland Amanda、McRaven Michael D.、Matias Edgar、Taylor Roslyn A.、Rogers Kenneth A.、Kulkarni Viraj、Gupta Sandeep、Thomas Yanique、Hope Thomas J.
Department of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine||Center for Pathogen Genomics and Microbial Evolution, Northwestern University Institute for Global HealthDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Biology, New Iberia Research Center, University of Louisiana at LafayetteDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio||Disease Intervention and Prevention, Texas Biomedical Research InstituteDepartment of Biology, New Iberia Research Center, University of Louisiana at LafayetteDepartment of Biology, New Iberia Research Center, University of Louisiana at Lafayette||Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio||Disease Intervention and Prevention, Texas Biomedical Research InstituteDisease Intervention and Prevention, Texas Biomedical Research InstituteDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Biology, New Iberia Research Center, University of Louisiana at LafayetteDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San AntonioDepartment of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio||Disease Intervention and Prevention, Texas Biomedical Research InstituteDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of MedicineDepartment of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine
医学研究方法基础医学儿科学
Allen Edward J.,Lorenzo-Redondo Ramon,Carias Ann M.,Anderson Meegan R.,Villinger Francois J,Lakhashe Samir,Ara¨anga Mariluz,Ruprecht Ruth M.,Strickland Amanda,McRaven Michael D.,Matias Edgar,Taylor Roslyn A.,Rogers Kenneth A.,Kulkarni Viraj,Gupta Sandeep,Thomas Yanique,Hope Thomas J..Localization of infection in neonatal rhesus macaques after oral viral challenge[EB/OL].(2025-03-28)[2025-06-24].https://www.biorxiv.org/content/10.1101/2021.07.30.454439.点此复制
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