title: Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice.
abstract: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis.
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Wu
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.|HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Cheung
authors.affiliation: HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing You'an Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Lu
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Allen Ka Loon
authors.initials: AK
authors.lastname: Cheung
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Liu
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Li
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.|Fuzhou Center for Disease Control and Prevention, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: Zhiwei W
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China.
authors.forename: Samantha M Y
authors.initials: SM
authors.lastname: Chen
authors.affiliation: Beijing You'an Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Beijing You'an Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: AIDS Institute and Department of Microbiology, Research Centre for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China. zchenai@hku.hk.|HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China. zchenai@hku.hk.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019562:Viral Load / Q000502:physiology
keywords: Acute infection; HAND; HIV-1; NSG; Transmitted/founder
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