Species specificity for transduction of cultured cells by a recombinant Lulll rodent parvovirus genome encapsidated by canine parvovirus or feline panleukopenia virus

Abstract

We previously reported that a recombinant genome derived from the autonomous rodent parvovirus Lulll could be pseudotyped with capsids of the closely related viruses, H 1 and minute virus of mice. To determine whether this was also possible with less related viruses, Lulll recombinant genomes containing a luciferase reporter were cotransfected into permissive cells together with plasmids expressing the capsid proteins of either feline panleukopenia virus (FPV) or its host range variant, canine parvovirus (CPV). We observed efficient packaging of the recombinant DNA into transducing virions that displayed the cell tropism of the virus that supplied the capsid. Thus, the FPV-and CPVpseudotyped virions were able to transduce a feline cell line but they showed no transducing activity for the human NB324K line, which is permissive for Lulll. The transducing activity of the pseudotyped viruses was not inhibited by neuraminidase treatment of the permissive recipient cells, in contrast to that of virions packaged using Lulll capsid proteins. Furthermore, canine A72 cells (permissive for CPV but not FPV) were efficiently transduced by CPVpackaged but not by FPV-packaged Lulll recombinant genomes. Pseudotyped recombinants will be useful for elucidating parvovirus host range determinants since they enable the packaged DNA and each of the capsid proteins to be supplied independently. They should also facilitate control over the targeting of parvovirus vectors for gene transfer.

Control of parvovirus DNA replication by a tetracycline-regulated repressor

“…These viruses include parvovirus H1 of rats, the minute virus of mice (MVM), and the closely related parvovirus LuIII (natural host unknown) which we have previously used to construct recombinant vectors. [7][8][9] There have been isolated reports of attempts to use parvovirus H1 for treatment of cancer patients. 10,11 The potential for therapeutic use of parvoviruses, based on their oncolytic properties, might be enhanced if NS1 expression and hence replication could be controlled by an appropriate drug.…”

Tropic determinant for canine parvovirus and feline panleukopenia virus functions through the capsid protein VP2.

“…Maxwell!uchsc.edu with substitution of reporter genes for the viral coding sequences . The recombinant genome could be packaged by capsid proteins either from LuIII or from related parvoviruses, including CPV or FPV (Maxwell et al, 1993 b ;Spitzer et al, 1996). In particular, packaging of the recombinant with capsid proteins supplied by a CPV helper, but not by a FPV helper, conferred the ability to transduce canine A72 cells efficiently (Spitzer et al, 1996).…”

“…The recombinant genome could be packaged by capsid proteins either from LuIII or from related parvoviruses, including CPV or FPV (Maxwell et al, 1993 b ;Spitzer et al, 1996). In particular, packaging of the recombinant with capsid proteins supplied by a CPV helper, but not by a FPV helper, conferred the ability to transduce canine A72 cells efficiently (Spitzer et al, 1996). By packaging a heterologous genome the results confirmed that the tropic determinants for CPV and FPV were specified by the capsid and direct involvement of the encoding DNA was excluded.…”

“…pGLuP38LUC2 retains the complete coding sequence for the NS proteins and can express the NS1 protein required for DNA amplification and P38 transactivation. Therefore, only a VP expression plasmid is necessary for recombinant virus production from pGLuP38LUC2 in transfected cells.The capsid protein expression plasmids, pC-VP and pF-VP (Spitzer et al, 1996), contain the P38 promoter and capsid coding sequences of CPV and FPV, respectively. These plasmids, which express both VP1 and VP2, are replicationdefective owing to deletion of one or both terminal palindromes and " 0n8-1n0 kb of the NS protein coding region.…”

“…The capsid protein expression plasmids, pC-VP and pF-VP (Spitzer et al, 1996), contain the P38 promoter and capsid coding sequences of CPV and FPV, respectively. These plasmids, which express both VP1 and VP2, are replicationdefective owing to deletion of one or both terminal palindromes and " 0n8-1n0 kb of the NS protein coding region.…”