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Regulation of Antiviral Innate Immunity Through APOBEC Ribonucleoprotein Complexes

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Macromolecular Protein Complexes II: Structure and Function

Part of the book series: Subcellular Biochemistry ((SCBI,volume 93))

Abstract

The DNA mutagenic enzyme known as APOBEC3G (A3G) plays a critical role in innate immunity to Human Immunodeficiency Virus-1 (HIV-1 ). A3G is a zinc-dependent enzyme that mutates select deoxycytidines (dC) to deoxyuridine (dU) through deamination within nascent single stranded DNA (ssDNA) during HIV reverse transcription. This activity requires that the enzyme be delivered to viral replication complexes by redistributing from the cytoplasm of infected cells to budding virions through what appears to be an RNA-dependent process. Once inside infected cells, A3G must bind to nascent ssDNA reverse transcripts for dC to dU base modification gene editing. In this chapter we will discuss data indicating that ssDNA deaminase activity of A3G is regulated by RNA binding to A3G and ribonucleoprotein complex formation along with evidence suggesting that RNA-selective interactions with A3G are temporally and mechanistically important in this process.

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Abbreviations

A3:

Collectively all APOBEC3 proteins, A3A, A3B, A3C, A3D, A3F, A3G, A3H

AID :

Activation induced deaminase

APOBEC :

Apolipoprotein B editing catalytic unit

CD1:

N-terminal domain of dual domain APOBEC proteins

CD2:

C-terminal domain of dual domain APOBEC proteins

CLIP-Seq:

Crosslinking immunoprecipitation and sequencing of RNA bound to proteins

gRNA:

HIV genomic RNA

HIV:

Human immunodeficiency virus

hY:

Human Y ncRNA

NC:

Nucleocapsid portion of HIV Gag

ncRNA:

Noncoding RNA

RNP:

Ribonucleoprotein particle

RT:

Reverse transcriptase

RNA-Seq:

RNA sequencing

ssDNA:

Single stranded DNA

ZBD:

Zinc binding domain

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Authors and Affiliations

  1. OyaGen, Inc, 77 Ridgeland Road, Rochester, NY, 14623, USA

    Jason D. Salter, Ryan P. Bennett & Harold C. Smith

  2. Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Ave, Rochester, NY, 14642, USA

    Bogdan Polevoda & Harold C. Smith

Authors
  1. Jason D. Salter
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  2. Bogdan Polevoda
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  3. Ryan P. Bennett
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  4. Harold C. Smith
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Correspondence to Harold C. Smith .

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Editors and Affiliations

  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, UK

    Jon Marles-Wright

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Salter, J.D., Polevoda, B., Bennett, R.P., Smith, H.C. (2019). Regulation of Antiviral Innate Immunity Through APOBEC Ribonucleoprotein Complexes. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes II: Structure and Function . Subcellular Biochemistry, vol 93. Springer, Cham. https://doi.org/10.1007/978-3-030-28151-9_6

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