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APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication

Qin Yu1, Darlene Chen, Renate König

  • 1Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

The Journal of Biological Chemistry
|October 7, 2004
PubMed

Insights

APOBEC3B and APOBEC3C exhibit antiviral activity against SIV, unlike HIV-1. SIV Vif protein counters APOBEC3C but not APOBEC3B, suggesting specific lentivirus neutralization by APOBEC3 family members.

Area of Science:

  • Genetics and Molecular Biology
  • Virology
  • Immunology

Background:

  • The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC)3 gene family in humans comprises APOBEC3A-G.
  • APOBEC3G and APOBEC3F show potent activity against human immunodeficiency virus 1 (HIV-1) lacking Vif (Deltavif).
  • Lentiviral Vif protein counteracts APOBEC3G and APOBEC3F by inducing their degradation.

Purpose of the Study:

  • To investigate the antiviral activity of APOBEC3B and APOBEC3C against simian immunodeficiency virus (SIV).
  • To determine the susceptibility of APOBEC3B and APOBEC3C to SIV Vif.
  • To explore the potential for differential neutralization of lentiviruses by various APOBEC3 family members.

Main Methods:

  • Encapsidation of APOBEC3B and APOBEC3C into HIV-1 and SIV virions.
  • Assessment of antiviral activity against Deltavif SIV(mac) and SIV(agm).
  • Analysis of G to A mutations in SIV reverse transcripts induced by APOBEC3B and APOBEC3C.

Main Results:

  • APOBEC3B and APOBEC3C demonstrated potent antiviral activity against SIV, but not HIV-1.
  • SIV Vif neutralized APOBEC3C's antiviral activity but not APOBEC3B's.
  • APOBEC3B induced significant G to A hypermutation in SIV reverse transcripts, while APOBEC3C induced fewer mutations.
  • APOBEC3F was active against SIV and susceptible to SIV(mac) Vif.

Conclusions:

  • APOBEC3B and APOBEC3C possess distinct antiviral profiles against SIV compared to HIV-1.
  • The differential interaction with SIV Vif suggests a mechanism for selective lentivirus neutralization by APOBEC3 family members.
  • These findings highlight the specialized roles of different APOBEC3 proteins in innate antiviral defense against lentiviruses.

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