Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Genome replication and postencapsidation functions mapping to the nonstructural gene restrict the host range of a murine parvovirus in human cells
Autore:
Rubio, MP; Guerra, S; Almendral, JM;
Indirizzi:
Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28049 o Ochoa, E-28049 Madrid, Spain
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 23, volume: 75, anno: 2001,
pagine: 11573 - 11582
SICI:
0022-538X(200112)75:23<11573:GRAPFM>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
MINK DISEASE PARVOVIRUS; INFECTIOUS VIRUS PRODUCTION; TRANSFORMED RAT-CELLS; MICE NS1 PROTEIN; MINUTE VIRUS; DNA-REPLICATION; PORCINE PARVOVIRUS; CANINE PARVOVIRUS; IN-VITRO; AUTONOMOUS PARVOVIRUSES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
90
Recensione:
Indirizzi per estratti:
Indirizzo: Almendral, JM Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28049 49 Madrid, Spain
Citazione:
M.P. Rubio et al., "Genome replication and postencapsidation functions mapping to the nonstructural gene restrict the host range of a murine parvovirus in human cells", J VIROLOGY, 75(23), 2001, pp. 11573-11582

Abstract

The infection outcome of the Parvoviridae largely relies on poorly characterized intracellular factors modulated by proliferation, differentiation, and transformation of host cells. We have studied the interactions displayedby the highly homologous p and i strains of the murine parvovirus minute virus of mice (MVM), with a series of transformed cells of rat (C6) and human (U373, U87, SW1088, SK-N-SH) nervous system origin, seeking for molecularmechanisms governing parvovirus host range. The MVMp infection of C6 and U373 cells was cytotoxic and productive, whereas the other nervous cells behaved essentially as resistant to this virus. In contrast, MVMi did not complete its life cycle in any of the human nervous cells, though it efficiently killed the astrocytic tumor cells by two types of nonproductive infections: (i) normal synthesis of all viral macromolecules with a late defect in infectious virion maturation and release to the medium in U373; and (ii) high levels of accumulation of the full set of viral messenger RNAs and of both nonstructural (NS-1) and structural (VP-1 and VP-2) proteins, under a very low viral DNA amplification, in U87 and SW1088 cells. Further analyses showed that U87 was permissive for nuclear transport of MVMi proteins, leading to efficient assembly of empty viral capsids with a normal phosphorylation and VP1-to-VP2 ratio. The DNA amplification blockade in U87 occurred after conversion of the incoming MVMi genome to the monomeric replicative form,and it operated independently of the delivery pathway used by the viral particle, since it could not be overcome by transfection with cloned infectious viral DNA. Significantly, a chimeric NVMi virus harboring the coding region of the nonstructural (NS) gene replaced with that of MVMp showed a similar pattern of restriction in U87 cells as the parental MVMi virus, and it attained in U373 cultures an infectious titer above 100-fold higher under equal levels of DNA amplification and genome encapsidation. The results suggest that the activity of complexes formed by the NS polypeptides and recruited cellular factors restrict parvovirus DNA amplification in a cell type-dependent manner and that NS functions may in addition determine MVM host range acting at postencapsidation steps of viral maturation. These data are relevant for understanding the increased multiplication of autonomous parvovirus in some transformed cells and the transduction efficacy of nonreplicative parvoviral vectors, as well as a general remark on the mechanisms by which NS genes may regulate viral tropism and pathogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 10:06:38