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 language | English (US) |
|---|---|
| Pages (from-to) | 7480-7484 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 92 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 1 1995 |
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Keywords
- dUTPase
- feline
- immunodeficiency
- lentivirus
- misincorporation
ASJC Scopus subject areas
- General
Cite this
Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase. / Lerner, Danica L.; Wagaman, Pamela C.; Phillips, Tom R.; Prospero-Garcia, Oscar; Henriksen, Steven J.; Fox, Howard S; Bloom, Floyd E.; Elder, John H.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 16, 01.08.1995, p. 7480-7484.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase
AU - Lerner, Danica L.
AU - Wagaman, Pamela C.
AU - Phillips, Tom R.
AU - Prospero-Garcia, Oscar
AU - Henriksen, Steven J.
AU - Fox, Howard S
AU - Bloom, Floyd E.
AU - Elder, John H.
PY - 1995/8/1
Y1 - 1995/8/1
N2 - 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.
AB - 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.
KW - dUTPase
KW - feline
KW - immunodeficiency
KW - lentivirus
KW - misincorporation
UR - http://www.scopus.com/inward/record.url?scp=0029153930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029153930&partnerID=8YFLogxK
U2 - 10.1073/pnas.92.16.7480
DO - 10.1073/pnas.92.16.7480
M3 - Article
VL - 92
SP - 7480
EP - 7484
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 16
ER -