Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution

Kimberly Schmitt; Kejun Guo; Malinda Algaier; Autumn Ruiz; Fang Cheng; Jianming Qiu; Silke Wissing; Mario L. Santiago; Edward B. Stephens

doi:10.1016/j.virol.2011.07.017

Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution

Kimberly Schmitt, Kejun Guo, Malinda Algaier, Autumn Ruiz, Fang Cheng, Jianming Qiu, Silke Wissing, Mario L. Santiago, Edward B. Stephens

Molecular Medicine

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

28 Scopus citations

Abstract

The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4⁺ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication.

Original language	English (US)
Pages (from-to)	24-42
Number of pages	19
Journal	Virology
Volume	419
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2011.07.017
State	Published - Oct 10 2011

Keywords

APOBEC3A
Evolution
HIV-1
Rhesus macaques
SHIV
Vif
Virus restriction

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2011.07.017

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@article{b5f9fc5920e146afa33ab025f4e885c4,

title = "Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution",

abstract = "The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication.",

keywords = "APOBEC3A, Evolution, HIV-1, Rhesus macaques, SHIV, Vif, Virus restriction",

author = "Kimberly Schmitt and Kejun Guo and Malinda Algaier and Autumn Ruiz and Fang Cheng and Jianming Qiu and Silke Wissing and Santiago, {Mario L.} and Stephens, {Edward B.}",

note = "Funding Information: The work reported here is supported by grants NIH AI090795 to M.L.S. and NIH AI51981 to E.B.S. We thank members of the KUMC Biotechnology Support Facility and Northwestern University for their assistance with the sequence analysis and oligonucleotide synthesis. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl from Dr. John C. Kappes, Dr. Xiaoyun Wu and Tranzyme Inc.; pNL4-3 from Dr. Malcolm Martin; and p24 antibody from Dr. Michael H. Malim.",

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doi = "10.1016/j.virol.2011.07.017",

language = "English (US)",

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T1 - Differential virus restriction patterns of rhesus macaque and human APOBEC3A

T2 - Implications for lentivirus evolution

AU - Schmitt, Kimberly

AU - Guo, Kejun

AU - Algaier, Malinda

AU - Ruiz, Autumn

AU - Cheng, Fang

AU - Qiu, Jianming

AU - Wissing, Silke

AU - Santiago, Mario L.

AU - Stephens, Edward B.

N1 - Funding Information: The work reported here is supported by grants NIH AI090795 to M.L.S. and NIH AI51981 to E.B.S. We thank members of the KUMC Biotechnology Support Facility and Northwestern University for their assistance with the sequence analysis and oligonucleotide synthesis. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl from Dr. John C. Kappes, Dr. Xiaoyun Wu and Tranzyme Inc.; pNL4-3 from Dr. Malcolm Martin; and p24 antibody from Dr. Michael H. Malim.

PY - 2011/10/10

Y1 - 2011/10/10

N2 - The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication.

AB - The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian-human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication.

KW - APOBEC3A

KW - Evolution

KW - HIV-1

KW - Rhesus macaques

KW - SHIV

KW - Vif

KW - Virus restriction

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SN - 0042-6822

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JF - Virology

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ER -

Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution

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