title: Functional Evidence of the Involvement of the Dynein Light Chain DYNLRB2 in Murine Leukemia Virus Infection.
abstract: How murine leukemia virus (MLV) travels from the cell membrane to the nucleus and the mechanism for nuclear entry of MLV DNA in dividing cells still remain unclear. It seems likely that the MLV preintegration complex (PIC) interacts with cellular proteins to perform these tasks. We recently published that the microtubule motor cytoplasmic dynein complex and its regulator proteins interact with the MLV PIC at early times of infection, suggesting a functional interaction between the incoming viral particles, the dynein complex, and dynein regulators. To better understand the role of the dynein complex in MLV infection, we performed short hairpin RNA (shRNA) screening of the dynein light chains on MLV infection. We found that silencing of a specific light chain of the cytoplasmic dynein complex, DYNLRB2, reduced the efficiency of infection by MLV reporter viruses without affecting HIV-1 infection. Furthermore, the overexpression of DYNLRB2 increased infection by MLV. We conclude that the DYNLRB2 light chain of the cytoplasmic dynein complex is an important and specific piece of the host machinery needed for MLV infection.IMPORTANCERetroviruses must reach the chromatin of their host to integrate their viral DNA, but first they must get into the nucleus. The cytoplasm is a crowded environment in which simple diffusion is slow, and thus viruses utilize retrograde transport along the microtubule network, mediated by the dynein complex. Different viruses use different components of this multisubunit complex. We have found that murine leukemia virus (MLV) associates functionally and specifically with the dynein light chain DYNLRB2, which is required for infection. Our study provides more insight into the molecular requirements for retrograde transport of the MLV preintegration complex and demonstrates, for the first time, a role for DYNLRB2 in viral infection.
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Opazo
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Garcés
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Tapia
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Barraza
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Angélica
authors.initials: A
authors.lastname: Bravo
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Tomás
authors.initials: T
authors.lastname: Schwenke
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cancino
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andres Bello, Viña del Mar, Chile gloria.arriagada@unab.cl.
authors.forename: Gloria
authors.initials: G
authors.lastname: Arriagada
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology; D056445:Cytoplasmic Dyneins / Q000235:genetics* / Q000502:physiology*; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000821:virology; D041681:NIH 3T3 Cells
chemical_list: D056445:Cytoplasmic Dyneins; C449283:DYNLRB2 protein, human
keywords: DYNLRB2; MLV; dynein; dynein light chain