title: Requirements for different components of the host cell cytoskeleton distinguish ecotropic murine leukemia virus entry via endocytosis from entry via surface fusion.
abstract: Murine ecotropic leukemia viruses use a common receptor for entry into host cells; however, the site of virus fusion appears to differ with the host cell. Entry in mouse NIH 3T3 fibroblasts is by endocytosis, whereas entry in rat XC sarcoma cells is by surface fusion. We report here the identification of a step common to both entry pathways, as well as of a step unique to the endocytic pathway. Recent demonstration of the clustering of the virus receptor on rat cells suggested a possible interaction of the receptor with the cellular cytoskeleton (M. H. Woodard, W. A. Dunn, R. O. Laine, M. Malandro, R. McMahon, O. Simell, E. R. Block, and M. S. Kilberg, Am. J. Physiol. 266:E817-E824, 1994). We tested the hypothesis that such an interaction might influence receptor function. We found that entry into NIH 3T3 and XC cells was greatly diminished by the disruption of the actin network before but not shortly after virus internalization, suggesting the actin network plays a critical role in an early step common to both entry pathways. Disruption of microtubules before and shortly after virus internalization markedly reduced entry in NIH 3T3 cells, while entry into XC cells remained efficient. These data suggest that intact microtubules are required in a postpenetration step unique to efficient virus entry via endocytosis. The physiological function of the receptor was not affected by disruption of either the actin network or the microtubules, as the uptake of cationic amino acids in NIH 3T3 and XC cells was comparable to that in control cells even when the cytoskeleton remained disrupted for as long as 3 h.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Tennessee-Memphis, 38163, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kizhatil
authors.forename: L M
authors.initials: LM
authors.lastname: Albritton
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D004705:Endocytosis; D009052:Leukemia Virus, Murine / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology*; D051381:Rats; D012513:Sarcoma, Experimental; D013997:Time Factors; D014404:Tubulin / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D014404:Tubulin; D015638:Cytochalasin D; D015739:Nocodazole