How Do Animal Dna Viruses Get to the Nucleus?

Abstract

Genome and pre-genome replication in all animal DNA viruses except poxviruses occurs in the cell nucleus (Table 1). In order to reproduce, an infecting virion enters the cell and traverses through the cytoplasm toward the nucleus. Using the cell's own nuclear import machinery, the viral genome then enters the nucleus through the nuclear pore complex. Targeting of the infecting virion or viral genome to the multiplication site is therefore an essential process in productive viral infection as well as in latent infection and transformation. Yet little is known about how infecting genomes of animal DNA viruses reach the nucleus in order to reproduce. Moreover, this nuclear locus for viral multiplication is remarkable in that the sizes and composition of the infectious particles vary enormously. In this article, we discuss virion structure, life cycle to reproduce infectious particles, viral protein's nuclear import signal, and viral genome nuclear targeting.

Utilization of synthetic peptides containing nuclear localization signals for nonviral gene transfer systems

“…The general proof of this concept is provided by the fact that some viruses, among them DNA viruses, as part of their life cycle transport their genome through the nuclear pore complex (NPC), probably by interaction with the cellular nuclear import machinery. 19,20 However, this crucial translocation step of the viral DNA is not completely understood, so that it cannot be transposed directly to nonviral gene transfer systems. Nevertheless, numerous efforts were made to modify plasmid DNA so that it can be recognized by cellular factors as a nuclear import substrate.…”

Protein Transduction Domain of HIV-1 Tat Protein Promotes Efficient Delivery of DNA into Mammalian Cells

“…This schema also essentially describes the genome delivery of karyophilic recombinant viruses (3). Differences in the efficacy of viral and nonviral vectors reside partly in the mechanisms by which they deliver genes across the plasma membrane (2).…”

“…In contrast, most nonviral vehicles deliver their genes passively, relying on uptake into the vesicular compartments by endocytosis. A detailed understanding of the intracellular mechanisms of virus infection (nuclear transport of the viral genome and subsequent disassembly of the DNAprotein complex) has yet to be achieved (3). Therefore, most current efforts to refine nonviral delivery systems by mimicking viral functions focus on the first three stages.…”

Adeno-associated virus vectors: potential applications for cancer gene therapy

“…20,21 Perinuclear accumulation appears to be problematic for both permissive and nonpermissive cells, suggesting that the process of nuclear entry may also affect vector transduction in certain cell types. 22 After receptor binding, internalization, and nuclear entry, AAV virions uncoat and release a single-stranded DNA template, which must be converted to a duplex intermediate before transcription can ensue. The efficiency of forming the complementary strand can significantly impact vector transduction.…”