An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer.
Direct RNA-PCR analyses of T-cell lymphomas that developed in rhesus macaques during a gene transfer experiment revealed the presence of several different recombinant murine leukemia viruses (MuLV). Most prominent was the expected MuLV recombinant, designated MoLTRAmphoenv in which the amphotropic env of the helper packaging virus was joined to the long terminal repeat (LTR) of the Moloney MuLV-derived vector. This retrovirus does not exist in nature. An additional copy of the core enhancer acquired from the vector LTR may have augmented the replicative properties of MoLTRAmphoenv MuLV in several different rhesus cell types compared with the prototype amphotropic MuLV4070A. Unexpectedly, at least two types of mink cell focus-forming MuLV elements, arising from endogenous retroviral sequences expressed in the murine packaging cell line, were also transmitted and highly expressed in one of the macaques. Furthermore, murine virus-like VL-30 sequences were detected in the rhesus lymphomas, but these were not transcribed into RNA. The unanticipated presence of an array of MuLV-related structures in a primate gene transfer recipient demands ever-vigilant scrutiny for the existence of transmissible retroviral elements and replication-competent viruses possessing altered tropic or growth properties in packaging cells producing retroviral vectors.
Purcell
D F
DF
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Broscius
C M
CM
Vanin
E F
EF
Buckler
C E
CE
Nienhuis
A W
AW
Martin
M A
MA
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004279:DNA, Viral; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D015752:Genes, env; D005822:Genetic Vectors; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D008223:Lymphoma / Q000821:virology*; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012192:Retroviridae Infections / Q000821:virology*; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics; D014779:Virus Replication
D004279:DNA, Viral; D014759:Viral Envelope Proteins