T-cell responses to sequentially emerging viral escape mutants shape long-term HIV-1 population dynamics

Autor: Chanson J. Brumme, Nozomi Kuse, Zabrina L. Brumme, Tomohiro Akahoshi, Hayato Murakoshi, Takayuki Chikata, Masafumi Takiguchi, Shinichi Oka, Naoki Ishizuka, Madoka Koyanagi, Hiroyuki Gatanaga
Rok vydání: 2020
Předmět:
RNA viruses
Heredity
Epitopes
T-Lymphocyte
HIV Infections
medicine.disease_cause
Host Adaptation
Virus Replication
Pathology and Laboratory Medicine
Epitope
Geographical Locations
White Blood Cells
0302 clinical medicine
Immunodeficiency Viruses
Japan
Animal Cells
HIV Seropositivity
Medicine and Health Sciences
Cytotoxic T cell
Biology (General)
Cells
Cultured
Staining
0303 health sciences
Mutation
education.field_of_study
T Cells
Cell Staining
Viral Load
Antigenic Variation
Genetic Mapping
medicine.anatomical_structure
Medical Microbiology
Viral Pathogens
Host-Pathogen Interactions
Viruses
Amino Acid Analysis
Cellular Types
Pathogens
Research Article
Asia
QH301-705.5
T cell
Immune Cells
Population
Immunology
Cytotoxic T cells
Human leukocyte antigen
Biology
Research and Analysis Methods
Microbiology
Clonal Evolution
03 medical and health sciences
Virology
Retroviruses
medicine
Genetics
Humans
education
Molecular Biology Techniques
Microbial Pathogens
Molecular Biology
030304 developmental biology
Immune Evasion
Molecular Biology Assays and Analysis Techniques
Blood Cells
Haplotype
Lentivirus
Organisms
Biology and Life Sciences
HIV
Cell Biology
RC581-607
Viral Replication
Molecular Typing
Viral replication
Haplotypes
Specimen Preparation and Treatment
People and Places
HIV-1
Parasitology
Immunologic diseases. Allergy
030215 immunology
HeLa Cells
T-Lymphocytes
Cytotoxic
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 16, Iss 12, p e1009177 (2020)
ISSN: 1553-7374
Popis: HIV-1 strains harboring immune escape mutations can persist in circulation, but the impact of selection by multiple HLA alleles on population HIV-1 dynamics remains unclear. In Japan, HIV-1 Reverse Transcriptase codon 135 (RT135) is under strong immune pressure by HLA-B*51:01-restricted and HLA-B*52:01-restricted T cells that target a key epitope in this region (TI8; spanning RT codons 128–135). Major population-level shifts have occurred at HIV-1 RT135 during the Japanese epidemic, which first affected hemophiliacs (via imported contaminated blood products) and subsequently non-hemophiliacs (via domestic transmission). Specifically, threonine accumulated at RT135 (RT135T) in hemophiliac and non-hemophiliac HLA-B*51:01+ individuals diagnosed before 1997, but since then RT135T has markedly declined while RT135L has increased among non-hemophiliac individuals. We demonstrated that RT135V selection by HLA-B*52:01-restricted TI8-specific T-cells led to the creation of a new HLA-C*12:02-restricted epitope TN9-8V. We further showed that TN9-8V-specific HLA-C*12:02-restricted T cells selected RT135L while TN9-8T-specific HLA-C*12:02-restricted T cells suppressed replication of the RT135T variant. Thus, population-level accumulation of the RT135L mutation over time in Japan can be explained by initial targeting of the TI8 epitope by HLA-B*52:01-restricted T-cells, followed by targeting of the resulting escape mutant by HLA-C*12:02-restricted T-cells. We further demonstrate that this phenomenon is particular to Japan, where the HLA-B*52:01-C*12:02 haplotype is common: RT135L did not accumulate over a 15-year longitudinal analysis of HIV sequences in British Columbia, Canada, where this haplotype is rare. Together, our observations reveal that T-cell responses to sequentially emerging viral escape mutants can shape long-term HIV-1 population dynamics in a host population-specific manner.
Author summary HIV-1 strains harboring immune escape mutations can accumulate in circulation, but it remains unclear to what extent these 'escaped' HIV-1 strains continue to evolve under ongoing population-level immune pressures. We investigated population-level changes at HIV-1 Reverse Transcriptase codon 135 (RT135), which is under pressure by T cells restricted by HLA-B*51:01 and B*52:01, highly frequent alleles in Japan. While threonine initially accumulated at RT135, RT135L has subsequently increased markedly. Our findings revealed that RT135V selection by HLA-B*52:01-restricted T-cells led to the creation of a new epitope restricted by HLA-C*12:02, an allele in strong linkage disequilibrium with HLA-B*52:01. HLA-C*12:02-restricted T cells in turn suppressed replication of RT135T virus and selected RT135L. Notably, population-level shifts at this codon are particular to Japan, where HLA-B*52:01-C*12:02 represents the most prevalent HLA haplotype. Our findings highlight multiple virus-specific T cells as dynamic drivers of population-level − and host population-specific − HIV-1 evolution over the long term.
Databáze: OpenAIRE
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