title: Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.
abstract: Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection.
authors: Center for AIDS Research, Kumamoto University, Kumamoto, Japan. Electronic address: tetsuo.tsukamoto@08.alumni.u-tokyo.ac.jp.
authors: Tetsuo
authors: T
authors: Tsukamoto
authors: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Yamamoto
authors: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors: Seiji
authors: S
authors: Okada
authors: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan; The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Tetsuro
authors: T
authors: Matano
mesh_terms: D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016679:Genome, Viral; D006678:HIV / Q000472:pathogenicity / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008251:Macaca; D008285:Major Histocompatibility Complex; D009154:Mutation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D013269:Stochastic Processes; D014766:Viremia / Q000276:immunology*; D014779:Virus Replication