Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations

Wei Wei; Haoran Guo; Min Ma; Richard Markham; Xiao Fang Yu

doi:10.1016/j.ebiom.2016.04.020

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations

Wei Wei, Haoran Guo, Min Ma, Richard Markham, Xiao Fang Yu

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.

Original language	English (US)
Pages (from-to)	230-236
Number of pages	7
Journal	EBioMedicine
Volume	8
DOIs	https://doi.org/10.1016/j.ebiom.2016.04.020
State	Published - Jun 1 2016

Keywords

Capsid variants
HIV-1
MxB
Positive selection

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.ebiom.2016.04.020

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title = "Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations",

abstract = "Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.",

keywords = "Capsid variants, HIV-1, MxB, Positive selection",

author = "Wei Wei and Haoran Guo and Min Ma and Richard Markham and Yu, {Xiao Fang}",

note = "Funding Information: This work was supported in part by funding from the Chinese Ministry of Science and Technology (No 2012CB911100 ), the Chinese Ministry of Education (No IRT1016 ). The funding sources had no role in the writing of the manuscript or the decision to submit for publication. We would like to acknowledge support for the statistical analysis from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health through Grant Number 1UL1TR001079 . The authors were not paid to write this article by any pharmaceutical company or agency. Publisher Copyright: {\textcopyright} 2016.",

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AU - Wei, Wei

AU - Guo, Haoran

AU - Ma, Min

AU - Markham, Richard

AU - Yu, Xiao Fang

N1 - Funding Information: This work was supported in part by funding from the Chinese Ministry of Science and Technology (No 2012CB911100 ), the Chinese Ministry of Education (No IRT1016 ). The funding sources had no role in the writing of the manuscript or the decision to submit for publication. We would like to acknowledge support for the statistical analysis from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health through Grant Number 1UL1TR001079 . The authors were not paid to write this article by any pharmaceutical company or agency. Publisher Copyright: © 2016.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.

AB - Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution.

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KW - Positive selection

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Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations

Abstract

Keywords

ASJC Scopus subject areas

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