title: HIV-1 and HIV-2 exhibit similar mutation frequencies and spectra in the absence of G-to-A hypermutation.
abstract: BACKGROUND
  Human immunodeficiency virus type 2 (HIV-2) is often distinguished clinically by lower viral loads, reduced transmissibility, and longer asymptomatic periods than for human immunodeficiency virus type 1 (HIV-1). Differences in the mutation frequencies of HIV-1 and HIV-2 have been hypothesized to contribute to the attenuated progression of HIV-2 observed clinically.
  
  
  RESULTS
  To address this hypothesis, we performed Illumina sequencing of multiple amplicons prepared from cells infected with HIV-1 or HIV-2, resulting in ~4.7 million read pairs and the identification of ~200,000 mutations after data processing. We observed that: (1) HIV-2 displayed significantly lower total mutation, substitution, and transition mutation frequencies than that of HIV-1, along with a mutation spectrum markedly less biased toward G-to-A transitions, (2) G-to-A hypermutation consistent with the activity of APOBEC3 proteins was observed for both HIV-1 and HIV-2 despite the presence of Vif, (3) G-to-A hypermutation was significantly higher for HIV-1 than for HIV-2, and (4) HIV-1 and HIV-2 total mutation frequencies were not significantly different in the absence of G-to-A hypermutants.
  
  
  CONCLUSIONS
  Taken together, these data demonstrate that HIV-2 exhibits a distinct mutational spectrum and a lower mutation frequency relative to HIV-1. However, the observed differences were primarily due to reduced levels of G-to-A hypermutation for HIV-2. These findings suggest that HIV-2 may be less susceptible than HIV-1 to APOBEC3-mediated hypermutation, but that the fidelities of other mutational sources (such as reverse transcriptase) are relatively similar for HIV-1 and HIV-2. Overall, these data imply that differences in replication fidelity are likely not a major contributing factor to the unique clinical features of HIV-2 infection.
authors.affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA. rawso018@umn.edu.|Molecular, Cellular, Developmental Biology and Genetics Graduate Program, University of Minnesota, Minneapolis, MN, USA. rawso018@umn.edu.
authors.forename: Jonathan M O
authors.initials: JM
authors.lastname: Rawson
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA. landman@cs.umn.edu.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Landman
authors.affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA. cavanr@biostat.umn.edu.|Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. cavanr@biostat.umn.edu.
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.affiliation: Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA. mansky@umn.edu.|Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA. mansky@umn.edu.|Department of Microbiology, University of Minnesota, Minneapolis, MN, USA. mansky@umn.edu.|Molecular, Cellular, Developmental Biology and Genetics Graduate Program, University of Minnesota, Minneapolis, MN, USA. mansky@umn.edu.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Mansky
mesh_terms: D000071478:APOBEC Deaminases; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics; D016334:Genes, vpr; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D015498:HIV-2 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D059645:Mutation Rate; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D014779:Virus Replication / Q000235:genetics*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054320:vif Gene Products, Human Immunodeficiency Virus; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase