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Moloney murine leukemia virus glyco-gag facilitates xenotropic murine leukemia virus-related virus replication through human APOBEC3-independent mechanisms
- Source :
- Retrovirology, Vol 9, Iss 1, p 58 (2012), Nitta, Takayuki; Lee, Sangouk; Ha, Dat; Arias, Maribel; Kozak, Christine A; & Fan, Hung. (2012). Moloney murine leukemia virus glyco-gag facilitates xenotropic murine leukemia virus-related virus replication through human APOBEC3-independent mechanisms. Retrovirology, 9(1), 58. doi: http://dx.doi.org/10.1186/1742-4690-9-58. Retrieved from: http://www.escholarship.org/uc/item/6vw9d7kg, Retrovirology
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Background One of the unique features of gammaretroviruses is that they contain an additional extended form of Gag, glyco-gag, which initiates in the leader sequence. MuLV glyco-gag, gPr80Gag, promotes retrovirus replication and disease progression. Although virtually all infectious MuLVs encode glyco-gag, XMRV (xenotropic murine leukemia virus-related virus) lacks the classical gPr80Gag sequence. We examined XMRV to determine if its leader sequence contains glyco-gag activity, whether the presence of conventional gPr80Gag affects replication of XMRV, and we describe the evolution of glyco-gag-deficient MuLVs in Mus. Results We introduced several mutations disrupting two putative but noncanonical glyco-gag proteins in the leader sequence region in XMRV and found that those mutations did not affect virus release nor susceptibility to the antiviral activity of hA3G (human APOBEC3G). A chimeric XMRV encoding the Moloney MuLV (M-MuLV) leader sequence (MXMRV) demonstrated that M-MuLV glyco-gag facilitated MXMRV release and increased infectivity. Infectivity assays with several cell lines showed that glyco-gag increases XMRV infectivity in all cell lines tested, but the level of this increase varies in different cell lines. Because MuLV glyco-gag counteracts mouse APOBEC3, we investigated whether M-MuLV glyco-gag enhances XMRV infection by counteracting human APOBEC3. Comparison of hAPOBEC3 isoforms expressed in different cell lines indicated that hA3B was the most likely candidate for a restrictive hA3. However over-expression of hA3B showed no enhanced restriction of infection by XMRV compared to MXMRV. Endogenous MuLVs in the sequenced mouse genome were screened for canonical glyco-gag, which was identified in two clades of xenotropic MuLVs (X-MuLVs) and ecotropic MuLVs, but not in other X-MuLVs or in any polytropic MuLVs. Conclusions M-MuLV glyco-gag facilitates XMRV replication, and the leader sequence region in XMRV does not encode proteins equivalent to M-MuLV glyco-gag. The fact that the ability of glyco-gag to enhance XMRV infection varies in different cell lines suggests a glyco-gag sensitive restrictive factor that further reduces XMRV infectivity. The M-MuLV glyco-gag enhancement for XMRV replication is through a hAPOBEC3 independent mechanism. The absence of glyco-gag in MuLVs carried by western European mice suggests that loss of this sequence is a relatively recent event with limited subspecies distribution.
- Subjects :
- M-MuLV
Glycosylation
Xenotropic murine leukemia virus-related virus
viruses
Virus Replication
urologic and male genital diseases
medicine.disease_cause
Cytosine Deaminase
Mice
Retrovirus
hemic and lymphatic diseases
Murine leukemia virus
glyco-gag
APOBEC Deaminases
APOBEC3G
Phylogeny
Genetics
Infectivity
0303 health sciences
Mutation
Restrictive factor
biology
030302 biochemistry & molecular biology
virus diseases
APOBEC3
Hep G2 Cells
3. Good health
Isoenzymes
Infectious Diseases
lcsh:Immunologic diseases. Allergy
Molecular Sequence Data
Gene Products, gag
Genome, Viral
Virus
Evolution, Molecular
03 medical and health sciences
Cytidine Deaminase
Virology
medicine
Animals
Humans
Amino Acid Sequence
Glycoproteins
030304 developmental biology
Base Sequence
Research
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
Rats
HEK293 Cells
Viral replication
Mutagenesis, Site-Directed
Virus release
XMRV
Moloney murine leukemia virus
lcsh:RC581-607
HeLa Cells
Subjects
Details
- ISSN :
- 17424690
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Retrovirology
- Accession number :
- edsair.doi.dedup.....83047aa6c0cfe8fcb05d930353b9ca8d