Intracellular trafficking of retroviral vectors: obstacles and advances

Visualization of targeted transduction by engineered lentiviral vectors

“…The endocytosed viruses are internalized through endocytic compartments, and the viruses fuse with the endosomal membrane to release viral genome into host cells. [20][21][22][23] During these processes, viruses utilize microtubule networks for movement toward the perinuclear regions. 24,25 Recent studies have shown that intracellular virus trafficking is critically involved in the endosomemediated sorting and transport of influenza virus, vesicular stomatitis virus (VSV) and Semliki Forest virus.…”

Intracellular partitioning of cell organelles and extraneous nanoparticles during mitosis

“…For ASV, the factors which translocate their PICs into the nucleus of (non)dividing cells are speculated or unknown e.g. an NLS in the ASV integrase protein may underlie PIC import [132]. In contrast to MuLV, lentiviruses and FV vectors showed a long-term persistence of a stable transduction intermediate in quiescent cells, so that they efficiently transduced G 0 fibroblasts which were later stimulated to divide [129].…”

“…Aside from lentiviruses, also other retroviruses such as ASV and FV enter the nuclei of nondividing cells, albeit less efficiently than that of dividing cells [129,132]. Recently, the FV group-specific antigen (Gag) was found to be the essential linker between the viral DNA in the PICs via its Cterminus and host chromosomes during mitosis through interaction with H2A/H2B histones via its Nterminus [143,144].…”

“…MuLV PICs perhaps lack NLSs or fail to display NLSs due to MuLV capsid, preventing their NPC import. Alternatively, the MuLV capsid may sterically hinder NPC import [132]. For that reason, MuLV PICs bind the host chromosomes during mitosis and are subsequently enclosed together with them in the daughter nuclei.…”

“…Murine leukemia virus (MuLV) (p12) [133,134] Human immunodeficiency virus (HIV) (LEDGF/p75) [141] Avian sarcoma virus (ASV) (IN) [132] Foamy virus (FV) (Gag) [143,144] Epstein Barr virus (EBV) EBNA1 [147][148][149] Kaposi sarcoma-associated herpesvirus (KSHV) LANA [151,152,154] Bovine (BPV) and human papillomavirus (HPV) E2 [155][156][157][158] Simian vacuolating virus 40 (SV40) unknown [161,162] …”