Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase

Danica L. Lerner, Pamela C. Wagaman, Tom R. Phillips, Oscar Prospero-Garcia, Steven J. Henriksen, Howard S. Fox, Floyd E. Bloom, John H. Elder

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine- triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse transcriptase and integrase in the pol gene. Here, we report the in vivo infection of cats with a DU- variant of the PPR strain of FIV and compare its growth properties and tissue distribution with those of wild-type FIV- PPR. The results reveal several important points: (i) DU- FIV is able to infect the cat, with kinetics similar to that observed with wild-type FIV; (ii) both wild-type and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody response which is able to limit the virus burden in both groups of animals; (iii) the virus burden is reduced in the DU- FIV- infected cats, particularly in tissues such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs integrated in the DNA of primary macrophages after 9 months of infection is ≃5-fold greater than the frequency observed in DU- FIV DNA integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV are G → A base changes, consistent with an increased misincorporation of deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because this enzyme is absent from human immunodeficiency virus type 1 and other primate lentiviruses, virus replication in cell environments with low DU activity may lead to increased mutation and contribute to the rapid expansion of the viral repertoire.

Original languageEnglish (US)
Pages (from-to)7480-7484
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number16
DOIs
StatePublished - Aug 1 1995

Keywords

  • dUTPase
  • feline
  • immunodeficiency
  • lentivirus
  • misincorporation

ASJC Scopus subject areas

  • General

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