For Yue Tso1,2, Ashley Sawyer1,2, Eun Hee Kwon1,2, Victor Mudenda3, Dianne Langford4, You Zhou5, John West1,2, Charles Wood1,2. 1. Nebraska Center for Virology. 2. School of Biological Sciences. 3. Department of Microbiology and Pathology, University Teaching Hospital, Lusaka, Zambia. 4. Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania. 5. Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, Nebraska.
Abstract
Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), one of the leading cancers in human immunodeficiency virus (HIV)-infected patients in Zambia. KSHV was detected in the human central nervous system (CNS) by polymerase chain reaction (PCR) analysis, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV-positive individuals by KSHV, we sought to determine whether the central nervous system (CNS) can be infected by KSHV in HIV-positive Zambian individuals. Methods: Postmortem brain tissue specimens were collected from individuals coinfected with KSHV and HIV. PCR and Southern blots were performed on DNA extracted from the brain tissue specimens to verify KSHV infection. Immunohistochemical analysis and immunofluorescent microscopy were used to localize and identify KSHV-infected cells. Tropism was further established by in vitro infection of primary human neurons with rKSHV.219. Results: KSHV DNA was detected in the CNS from 4 of 11 HIV-positive individuals. Immunohistochemical analysis and immunofluorescent microscopy demonstrated that KSHV infected neurons and oligodendrocytes in parenchymal brain tissues. KSHV infection of neurons was confirmed by in vitro infection of primary human neurons with rKSHV.219. Conclusion: Our study showed that KSHV infects human CNS-resident cells, primarily neurons, in HIV-positive Zambian individuals.
Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), one of the leading cancers in humanimmunodeficiency virus (HIV)-infectedpatients in Zambia. KSHV was detected in the human central nervous system (CNS) by polymerase chain reaction (PCR) analysis, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV-positive individuals by KSHV, we sought to determine whether the central nervous system (CNS) can be infected by KSHV in HIV-positive Zambian individuals. Methods: Postmortem brain tissue specimens were collected from individuals coinfected with KSHV and HIV. PCR and Southern blots were performed on DNA extracted from the brain tissue specimens to verify KSHV infection. Immunohistochemical analysis and immunofluorescent microscopy were used to localize and identify KSHV-infected cells. Tropism was further established by in vitro infection of primary human neurons with rKSHV.219. Results:KSHV DNA was detected in the CNS from 4 of 11 HIV-positive individuals. Immunohistochemical analysis and immunofluorescent microscopy demonstrated that KSHV infected neurons and oligodendrocytes in parenchymal brain tissues. KSHV infection of neurons was confirmed by in vitro infection of primary human neurons with rKSHV.219. Conclusion: Our study showed that KSHV infects human CNS-resident cells, primarily neurons, in HIV-positive Zambian individuals.
Authors: N S Brink; Y Sharvell; M R Howard; J D Fox; M J Harrison; R F Miller Journal: J Neurol Neurosurg Psychiatry Date: 1998-08 Impact factor: 10.154
Authors: Veenu Minhas; Brad P Brayfield; Kay L Crabtree; Chipepo Kankasa; Charles D Mitchell; Charles Wood Journal: BMC Infect Dis Date: 2010-05-12 Impact factor: 3.090
Authors: Alison M Elliott; Denise Whitby; Robert Newton; Katie Wakeham; Emily L Webb; Ismail Sebina; Lawrence Muhangi; Wendell Miley; W Thomas Johnson; Juliet Ndibazza Journal: Infect Agent Cancer Date: 2011-09-30 Impact factor: 2.965
Authors: Meilan He; Fan Cheng; Suzane Ramos da Silva; Brandon Tan; Océane Sorel; Marion Gruffaz; Tingting Li; Shou-Jiang Gao Journal: Cancer Treat Res Date: 2019
Authors: For Yue Tso; Andrew V Kossenkov; Salum J Lidenge; Owen Ngalamika; John R Ngowi; Julius Mwaiselage; Jayamanna Wickramasinghe; Eun Hee Kwon; John T West; Paul M Lieberman; Charles Wood Journal: PLoS Pathog Date: 2018-01-19 Impact factor: 6.823
Authors: Salum J Lidenge; For Yue Tso; Owen Ngalamika; Jaydeep Kolape; John R Ngowi; Julius Mwaiselage; Charles Wood; John T West Journal: Oncotarget Date: 2020-04-28