title: Selective infection of CD4+ effector memory T lymphocytes leads to preferential depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL-2Rgammanull mice.
abstract: To investigate the events leading to the depletion of CD4(+) T lymphocytes during long-term infection of human immunodeficiency virus type 1 (HIV-1), we infected human CD34(+) cells-transplanted NOD/SCID/IL-2Rgamma(null) mice with CXCR4-tropic and CCR5-tropic HIV-1. CXCR4-tropic HIV-1-infected mice were quickly depleted of CD4(+) thymocytes and both CD45RA(+) naïve and CD45RA(-) memory CD4(+) T lymphocytes, while CCR5-tropic HIV-1-infected mice were preferentially depleted of CD45RA(-) memory CD4(+) T lymphocytes. Staining of HIV-1 p24 antigen revealed that CCR5-tropic HIV-1 preferentially infected effector memory T lymphocytes (T(EM)) rather than central memory T lymphocytes. In addition, the majority of p24(+) cells in CCR5-tropic HIV-1-infected mice were activated and in cycling phase. Taken together, our findings indicate that productive infection mainly takes place in the activated T(EM) in cycling phase and further suggest that the predominant infection in T(EM) would lead to the depletion of memory CD4(+) T lymphocytes in CCR5-tropic HIV-1-infected mice.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Chuanyi
authors.initials: C
authors.lastname: Nie
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kitayama
authors.forename: Hisanori
authors.initials: H
authors.lastname: Fujino
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D019562:Viral Load
chemical_list: D012367:RNA, Viral