Early and transient reverse transcription during primary deltaretroviral infection of sheep.
BACKGROUND
Intraindividual genetic variability plays a central role in deltaretrovirus replication and associated leukemogenesis in animals as in humans. To date, the replication of these viruses has only been investigated during the chronic phase of the infection when they mainly spread through the clonal expansion of their host cells, vary through a somatic mutation process without evidence for reverse transcriptase (RT)-associated substitution. Primary infection of a new organism necessary involves allogenic cell infection and thus reverse transcription.


RESULTS
Here we demonstrate that the primary experimental bovine leukemia virus (BLV) infection of sheep displays an early and intense burst of horizontal replicative dissemination of the virus generating frequent RT-associated substitutions that account for 69% of the in vivo BLV genetic variability during the first 8 months of the infection. During this period, evidence has been found of a cell-to-cell passage of a mutated sequence and of a sequence having undergone both RT-associated and somatic mutations. The detection of RT-dependent proviral substitution was restricted to a narrow window encompassing the first 250 days following seroconversion.


CONCLUSIONS
In contrast to lentiviruses, deltaretroviruses display two time-dependent mechanisms of genetic variation that parallel their two-step nature of replication in vivo. We propose that the early and transient RT-based horizontal replication helps the virus escape the first wave of host immune response whereas somatic-dependent genetic variability during persistent clonal expansion helps infected clones escape the persistent and intense immune pressure that characterizes the chronic phase of deltaretrovirus infection.
Pomier
Carole
C
CNRS FRE3011-Université Claude Bernard, Oncovirologie et Biothérapies, Centre Léon Bérard, Lyon, France. ptepoms@yahoo.fr
Alcaraz
Maria T Sanchez
MT
Debacq
Christophe
C
Lançon
Agnes
A
Kerkhofs
Pierre
P
Willems
Lucas
L
Wattel
Eric
E
Mortreux
Franck
F
D000818:Animals; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D006800:Deltaretrovirus Infections / Q000821:virology*; D014644:Genetic Variation; D001909:Leukemia Virus, Bovine / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D009154:Mutation; D011533:Proviruses / Q000235:genetics; D048348:Reverse Transcription; D017422:Sequence Analysis, DNA; D012756:Sheep; D012757:Sheep Diseases / Q000821:virology*; D013997:Time Factors; D014779:Virus Replication
D004279:DNA, Viral