Generation of multiple replication-competent retroviruses through recombination between PreXMRV-1 and PreXMRV-2.

Abstract:

:We previously identified two novel endogenous murine leukemia virus proviruses, PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during xenograft passaging of a human prostate tumor in mice to generate xenotropic murine leukemia virus-related virus (XMRV). To determine the recombination potential of PreXMRV-1 and PreXMRV-2, we examined the generation of replication-competent retroviruses (RCRs) over time in a cell culture system. We observed that either virus alone was noninfectious and the RNA transcripts of the viruses were undetectable in the blood and spleen of nude mice that carry them. To determine their potential to generate RCRs through recombination, we transfected PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect fresh cells; the presence of reverse transcriptase activity at 10 days postinfection indicated the presence of RCRs. Population sequencing of proviral DNA indicated that all RCRs contained the gag and 5' half of pol from PreXMRV-2 and the long terminal repeat, 3' half of pol (including integrase), and env from PreXMRV-1. All crossovers were within sequences of at least 9 identical nucleotides, and crossovers within each of two selected recombination zones of 415 nucleotides (nt) in the 5' untranslated region and 982 nt in pol were required to generate RCRs. A recombinant with the same genotype as XMRV was not detected, and our analysis indicates that the probability of generating an identical RCR is vanishingly small. In addition, the studies indicate that the process of RCR formation is primarily driven by selection for viable cis and trans elements from the parental proviruses.

journal_name

J Virol

journal_title

Journal of virology

authors

Delviks-Frankenberry K,Paprotka T,Cingöz O,Wildt S,Hu WS,Coffin JM,Pathak VK

doi

10.1128/JVI.01787-13

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

11525-37

issue

21

eissn

0022-538X

issn

1098-5514

pii

JVI.01787-13

journal_volume

87

pub_type

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