Reduced proviral loads during primo-infection of sheep by Bovine Leukemia virus attenuated mutants.
BACKGROUND
The early stages consecutive to infection of sheep (e.g. primo-infection) by Bovine leukemia virus mutants are largely unknown. In order to better understand the mechanisms associated with this period, we aimed at analyzing simultaneously three parameters: B-lymphocytosis, cell proliferation and viral replication.


RESULTS
Sheep were experimentally infected either with a wild type BLV provirus or with selected mutants among which: a virus harboring an optimalized LTR promoter with consensus cyclic AMP-responsive elements, two deletants of the R3 or the G4 accessory genes and a fusion-deficient transmembrane recombinant. Seroconversion, as revealed by the onset of an anti-viral antibody response, was detected at 3 to 11 weeks after inoculation. At seroconversion, all sheep exhibited a marked increase in the numbers of circulating B lymphocytes expressing the CD5 and CD11b cluster of differentiation markers and, interestingly, this phenomenon occurred independently of the type of virus. The net increase of the absolute number of B cells was at least partially due to accelerated proliferation as revealed, after intravenous injection of bromodeoxyuridine, by the higher proportion of circulating BrdU+ B lymphocytes. BLV proviral DNA was detected by polymerase chain reaction in the leucocytes of all sheep, as expected. However, at seroconversion, the proviral loads were lower in sheep infected by the attenuated proviruses despite similar levels of B cell lymphocytosis.


CONCLUSIONS
We conclude that the proviral loads are not directly linked to the extent of B cell proliferation observed during primo-infection of BLV-infected sheep. We propose a model of opportunistic replication of the virus supported by a general activation process of B lymphocytes.
Debacq
Christophe
C
Molecular and cellular biology, FUSAGx, Gembloux, Belgium. debacq.c@fsagx.ac.be
Sanchez Alcaraz
Maria Teresa
MT
Mortreux
Franck
F
Kerkhofs
Pierre
P
Kettmann
Richard
R
Willems
Luc
L
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D016583:Enzootic Bovine Leukosis / Q000517:prevention & control; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D016130:Immunophenotyping; D001909:Leukemia Virus, Bovine / Q000235:genetics*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011533:Proviruses; D000644:Quaternary Ammonium Compounds; D012756:Sheep / Q000276:immunology; D012757:Sheep Diseases / Q000821:virology; D020079:Terminal Repeat Sequences; D019562:Viral Load / Q000662:veterinary*
D017931:DNA Primers; D004279:DNA, Viral; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D000644:Quaternary Ammonium Compounds; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane