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Abstract
BackgroundThe palindromic termini of parvoviruses have proven to play an essential role as origins of replication at different stages during the replication of their viral genome. Sequences from the left-end telomere of MVM form a functional origin on one side of the dimer replicative form intermediate. In contrast, the right-end origin can operate in its closed replicative form hairpin configuration or as a fully duplex linear sequence derived from either arm of a palindromic tetramer intermediate. To study the possibility that the LuIII left hairpin has a function in replication, comparable to that described for MVM, the replication of a minigenome containing two copies of the LuIII left terminus (LuIII Lt-Lt) was studied. ResultsThe data presented demonstrates that LuIII Lt-Lt was capable of replicating when NS1 helper functions were provided in trans. This extended hairpin, capable of acting as an origin of replication, lacks the arrangement of the specific domains present in the dimer duplex intermediate of MVM, the only active form of the left hairpin described for this parvovirus.ConclusionsThese findings suggest that the left hairpin of LuIII has an active NS1 driven origin of replication at this terminus in the double stranded extended form. This difference between LuIII and MVM has great implications on the replication of these viruses. The presence of origins of replication at both the left and right termini in their natural hairpin form can explain the unique encapsidation pattern observed for LuIII hinting on the mechanism used by this virus for the replication of its viral genome.
Highlights
The palindromic termini of parvoviruses have proven to play an essential role as origins of replication at different stages during the replication of their viral genome
Autonomous parvovirus replication and assembly occurs in the nucleus and is dependent upon host enzymes and cellular functions occurring during the S phase of the cell cycle [4,5,6]
The 3' hairpin serves as a primer, which allows a host polymerase to synthesize a complementary copy of the internal sequence of the viral genome until the growing strand reaches the folded back 5' terminus at the right end, resulting in a covalently closed DNA replicative form
Summary
The data presented demonstrates that LuIII Lt-Lt was capable of replicating when NS1 helper functions were provided in trans. This extended hairpin, capable of acting as an origin of replication, lacks the arrangement of the specific domains present in the dimer duplex intermediate of MVM, the only active form of the left hairpin described for this parvovirus
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