title: HIV-1 entry and trans-infection of astrocytes involves CD81 vesicles.
abstract: Astrocytes are extensively infected with HIV-1 in vivo and play a significant role in the development of HIV-1-associated neurocognitive disorders. Despite their extensive infection, little is known about how astrocytes become infected, since they lack cell surface CD4 expression. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. Astrocytes were found to bind and harbor virus followed by biphasic decay, with HIV-1 detectable out to 72 hours. HIV-1 was observed to associate with CD81-lined vesicle structures. shRNA silencing of CD81 resulted in less cell-associated virus but no loss of co-localization between HIV-1 and CD81. Astrocytes supported trans-infection of HIV-1 to T-cells without de novo virus production, and the virus-containing compartment required 37°C to form, and was trypsin-resistant. The CD81 compartment observed herein, has been shown in other cell types to be a relatively protective compartment. Within astrocytes, this compartment may be actively involved in virus entry and/or spread. The ability of astrocytes to transfer virus, without de novo viral synthesis suggests they are capable of sequestering and protecting virus and thus, they could potentially facilitate viral dissemination in the CNS.
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia ; Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
authors.forename: Lachlan R
authors.initials: LR
authors.lastname: Gray
authors.affiliation: The Kirby Institute, Darlinghurst, New South Wales, Australia.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Turville
authors.affiliation: The Kirby Institute, Darlinghurst, New South Wales, Australia.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Hitchen
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Cheng
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Ellett
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Hamid
authors.initials: H
authors.lastname: Salimi
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roche
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia ; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
authors.forename: Steve L
authors.initials: SL
authors.lastname: Wesselingh
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia ; Department of Infectious Diseases, Monash University, Victoria, Australia ; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia ; Department of Microbiology, Monash University, Victoria, Australia ; Department of Medicine, Monash University, Victoria, Australia.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Churchill
mesh_terms: D001253:Astrocytes / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D018920:Coculture Techniques; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D034622:RNA Interference; D013601:T-Lymphocytes / Q000821:virology; D013696:Temperature; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D022161:Transport Vesicles / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D060225:Tetraspanin 28