title: Rapid HIV-1 Disease Progression in Individuals Infected with a Virus Adapted to Its Host Population.
abstract: HIV-1 escape from CTL is predictable based on the Human Leukocyte Antigen (HLA) class I alleles expressed by the host. As such, HIV-1 sequences circulating in a population of hosts will harbor escape mutations specific to the HLA alleles of that population. In theory, this should increase the frequency of escape mutation transmission to persons expressing the restricting HLA allele, thereby compromising host immunity to the incoming HIV-1 strain. However, the clinical impact of infection with HIV-1 containing immune escape mutations has not conclusively been demonstrated. Japan's population features limited HLA diversity which is driving population-level HIV adaptation: for example, >60% of Japanese express HLA-A*24:02 and its associated Nef-Y135F escape mutation represents the population consensus. As such, Japan is an ideal population in which to examine this phenomenon. Here, we combine genetic and immunological analyses to identify A*24:02-positive individuals likely to have been infected with Y135F-containing HIV-1. Over a ~5 year follow-up, these individuals exhibited significantly lower CD4 counts compared to individuals inferred to have been infected with wild-type HIV-1. Our results support a significant negative clinical impact of pathogen adaptation to host pressures at the population level.
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo. Kashiwa-shi, Chiba, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Katoh
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kawana-Tachikawa
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Dayong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Chungyong
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Infectious Disease Control, the International Research Center for Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Koga
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Adachi
authors.affiliation: Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Koibuchi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.|British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.affiliation: Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo. Kashiwa-shi, Chiba, Japan.|Department of Infectious Disease Control, the International Research Center for Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Department of Infectious Diseases and Applied Immunology, Hospital, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.|Asian Research Center for Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
mesh_terms: D000220:Adaptation, Biological; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D017951:Antigen Presentation; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D012189:Retrospective Studies; D019562:Viral Load; D055815:Young Adult; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus