Cellular and viral determinants of retroviral nuclear entry

Can J Microbiol. 2016 Jan;62(1):1-15. doi: 10.1139/cjm-2015-0350. Epub 2015 Oct 16.

Abstract

Retroviruses must integrate their cDNA into the host genome to generate proviruses. Viral DNA-protein complexes interact with cellular proteins and produce pre-integration complexes, which carry the viral genome and cross the nuclear pore channel to enter the nucleus and integrate viral DNA into host chromosomal DNA. If the reverse transcripts fail to integrate, linear or circular DNA species such as 1- and 2-long terminal repeats are generated. Such complexes encounter numerous cellular proteins in the cytoplasm, which restrict viral infection and protect the nucleus. To overcome host cell defenses, the pathogens have evolved several evasion strategies. Viral proteins often contain nuclear localization signals, allowing entry into the nucleus. Among more than 1000 proteins identified as required for HIV infection by RNA interference screening, karyopherins, cleavage and polyadenylation specific factor 6, and nucleoporins have been predominantly studied. This review discusses current opinions about the synergistic relationship between the viral and cellular factors involved in nuclear import, with focus on the unveiled mysteries of the host-pathogen interaction, and highlights novel approaches to pinpoint therapeutic targets.

Keywords: 2-LTR; CPI; HIV-1; PIC; TNPO3; VIH-1; importation nucléaire; nuclear import.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Cell Nucleus / metabolism*
  • Gene Products, gag / physiology
  • Host-Pathogen Interactions*
  • Humans
  • Nuclear Pore Complex Proteins / physiology
  • Retroviridae / physiology*
  • Transcription Factors / physiology
  • Viral Proteins / metabolism
  • Virus Internalization
  • beta Karyopherins / physiology
  • mRNA Cleavage and Polyadenylation Factors / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Gene Products, gag
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • PSIP1 protein, human
  • TNPO3 protein, human
  • Transcription Factors
  • Viral Proteins
  • beta Karyopherins
  • cleavage factor Im, human
  • mRNA Cleavage and Polyadenylation Factors