title: Loss of virus-specific CD4(+) T cells with increases in viral loads in the chronic phase after vaccine-based partial control of primary simian immunodeficiency virus replication in macaques.
abstract: Virus-specific cellular immune responses play an important role in the control of immunodeficiency virus replication. However, preclinical trials of vaccines that induce virus-specific cellular immune responses have failed to contain simian immunodeficiency virus (SIV) replication in macaques. A defective provirus DNA vaccine system that efficiently induces virus-specific CD8(+) T-cell responses has previously been developed. The vaccinated macaques showed reduced viral loads, but failed to contain SIVmac239 replication. In this study, macaques that showed partial control of SIV replication were followed up to see if or how they lost this control in the chronic phase. Two of them showed increased viral loads about 4 or 8 months after challenge and finally developed AIDS. Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon (IFN-gamma) production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased. The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years. Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4(+) T cells in the chronic phase of SIV infection. Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Lun
authors.affiliation: Department of Microbiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Kano
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Mori
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.affiliation: Toyama Institute of Health, 17-1 Nakataikou-yama, Kosugi-machi, Imizu-gun, Toyama 939-0363, Japan.|AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Microbiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D015750:Genes, gag; D018655:Lymphocyte Count; D008252:Macaca fascicularis; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D013997:Time Factors; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D012367:RNA, Viral; D014765:Viral Vaccines