HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S. Harris, Yoshio Koyanagi, Kei Sato

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1.

Original languageEnglish
Article numbere1006348
JournalPLoS pathogens
Volume13
Issue number5
DOIs
Publication statusPublished - May 2017

Fingerprint

HIV-1
Viruses
Cytosine Deaminase
RNA Sequence Analysis
Viral RNA
Hematopoietic Stem Cells
Cell Culture Techniques
Phenotype
Pressure
Mutation
DNA
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Nakano, Y., Misawa, N., Juarez-Fernandez, G., Moriwaki, M., Nakaoka, S., Funo, T., ... Sato, K. (2017). HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation. PLoS pathogens, 13(5), [e1006348]. https://doi.org/10.1371/journal.ppat.1006348

HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation. / Nakano, Yusuke; Misawa, Naoko; Juarez-Fernandez, Guillermo; Moriwaki, Miyu; Nakaoka, Shinji; Funo, Takaaki; Yamada, Eri; Soper, Andrew; Yoshikawa, Rokusuke; Ebrahimi, Diako; Tachiki, Yuuya; Iwami, Shingo; Harris, Reuben S.; Koyanagi, Yoshio; Sato, Kei.

In: PLoS pathogens, Vol. 13, No. 5, e1006348, 05.2017.

Research output: Contribution to journalArticle

Nakano, Y, Misawa, N, Juarez-Fernandez, G, Moriwaki, M, Nakaoka, S, Funo, T, Yamada, E, Soper, A, Yoshikawa, R, Ebrahimi, D, Tachiki, Y, Iwami, S, Harris, RS, Koyanagi, Y & Sato, K 2017, 'HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation', PLoS pathogens, vol. 13, no. 5, e1006348. https://doi.org/10.1371/journal.ppat.1006348
Nakano, Yusuke ; Misawa, Naoko ; Juarez-Fernandez, Guillermo ; Moriwaki, Miyu ; Nakaoka, Shinji ; Funo, Takaaki ; Yamada, Eri ; Soper, Andrew ; Yoshikawa, Rokusuke ; Ebrahimi, Diako ; Tachiki, Yuuya ; Iwami, Shingo ; Harris, Reuben S. ; Koyanagi, Yoshio ; Sato, Kei. / HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation. In: PLoS pathogens. 2017 ; Vol. 13, No. 5.
@article{e8482be3f8b14a79842416e150561997,
title = "HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation",
abstract = "APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1.",
author = "Yusuke Nakano and Naoko Misawa and Guillermo Juarez-Fernandez and Miyu Moriwaki and Shinji Nakaoka and Takaaki Funo and Eri Yamada and Andrew Soper and Rokusuke Yoshikawa and Diako Ebrahimi and Yuuya Tachiki and Shingo Iwami and Harris, {Reuben S.} and Yoshio Koyanagi and Kei Sato",
year = "2017",
month = "5",
doi = "10.1371/journal.ppat.1006348",
language = "English",
volume = "13",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

AU - Nakano, Yusuke

AU - Misawa, Naoko

AU - Juarez-Fernandez, Guillermo

AU - Moriwaki, Miyu

AU - Nakaoka, Shinji

AU - Funo, Takaaki

AU - Yamada, Eri

AU - Soper, Andrew

AU - Yoshikawa, Rokusuke

AU - Ebrahimi, Diako

AU - Tachiki, Yuuya

AU - Iwami, Shingo

AU - Harris, Reuben S.

AU - Koyanagi, Yoshio

AU - Sato, Kei

PY - 2017/5

Y1 - 2017/5

N2 - APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1.

AB - APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1.

UR - http://www.scopus.com/inward/record.url?scp=85020233877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020233877&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1006348

DO - 10.1371/journal.ppat.1006348

M3 - Article

C2 - 28475648

AN - SCOPUS:85020233877

VL - 13

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 5

M1 - e1006348

ER -