Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis

摘要: Background Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition the plasma membrane. Release from MVB is thought occur by Ca(2+)-regulated fusion with Principal findings To address role of pathway replication murine leukemia virus (MLV) we took advantage mouse models for Hermansky-Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are characterized hypopigmentation immunological alterations that caused defects biogenesis trafficking MVBs other lysosome related organelles. Neonatal mice disease lacking functional AP-3, Rab27A BLOC factors were infected Moloney MLV spread bone marrow, spleen thymus was monitored. We found a moderate reduction infection levels most mutant mice, which differed less than two-fold compared wild-type mice. vitro, release form bone-marrow derived macrophages slightly enhanced. Finally, no evidence vitro. Furthermore, only moderately affected Synaptotagmin VII, Ca(2+)-sensor regulating Conclusions Given spreading depends on multiple rounds even at cellular level would accumulate lead significant effect over time. Thus our vivo vitro data collectively argue against an essential MVB- secretory lysosome-mediated egress MLV.