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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (16), p.7480-7484
• Main Authors: Lerner, D.L. (The Scripps Research Institute, La Jolla, CA.), Wagaman, P.C, Phillips, T.R, Prospero-Garcia, O, Henriksen, S.J, Fox, H.S, Bloom, F.E, Elder, J.H
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Antibodies; Base Sequence; BAZO; Biochemistry; Blood; Capsid - genetics; Capsid - immunology; Cats; CHAT; DEOXYRIBONUCLEOSIDE; DESOXIRIBONUCLEOSIDOS; DNA Primers - genetics; DNA, Viral - genetics; EXPERIMENTACION IN VIVO; EXPERIMENTATION IN VIVO; Feline Acquired Immunodeficiency Syndrome - virology; feline immunodeficiency virus; GATO; Genes, pol; Genetic mutation; Genome, Viral; GLANDE SALIVAIRE; GLANDULAS SALIVALES; HIDROLASAS; HIV; HYDROLASE; Immunity (Disease); Immunodeficiency Virus, Feline - enzymology; Immunodeficiency Virus, Feline - genetics; Immunodeficiency Virus, Feline - growth & development; INFECCION EXPERIMENTAL; INFECTION EXPERIMENTALE; Infections; LENTIVIRINAE; Leukocytes; LINFOCITOS; LYMPHOCYTE; MACROFAGOS; MACROPHAGE; Macrophages; Molecular Sequence Data; MUTACION; MUTANT; MUTANTES; MUTATION; Polymerase Chain Reaction; Pyrophosphatases - genetics; RATE; REPONSE IMMUNITAIRE; RESPUESTA INMUNOLOGICA; T lymphocytes; Tissue Distribution; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.16.7480

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 approximately 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 leads to 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