• The viral genome needs to get to the cytoplasm or to the nucleus for the virus that replicates in the nucleus. In other words, the viral nucleocapsid has to overcome two barriers (ie, plasma membrane and nuclear membrane).
  • Following attachment of the virus particle on the target cells, the next step is the penetration into the cytoplasm.
  • The mechanism for the penetration differs, whether enveloped or not.
  • For enveloped viruses, one of the following two mechanisms is used: direct fusion and receptor-mediated endocytosis.
  • For nonenveloped naked viruses, receptor-mediated endocytosis is used for penetration.
  • Direct fusion: Direct fusion, as its name implies, is a mechanism in which two membranes (ie, the viral envelope and cell membrane) fuse. In this case, the viral nucleocapsid is directly delivered to the cytoplasm, leaving the viral envelope behind on the plasma membrane. Retrovirus is a representative that penetrates by direct fusion.
  • Receptor-mediated endocytosis: Most viruses depend on endocytic uptakes, a process termed receptor-mediated endocytosis (See details here).

How do viruses overcome the plasma and nuclear membrane  barriers?

  • As stated above, most viruses enter the cell via receptor-mediated endocytosis. What would be the advantages of receptor-mediated endocytosis, as opposed to direct fusion?
  • Unlike direct fusion, evidently, receptor-mediated endocytosis bypasses the actin cortex or the meshwork of microfilaments in the cortex that presents an obstacle for the penetration. Moreover, by being taken up by endocytosis, animal viruses can avoid leaving the viral envelope glycoprotein on the plasma membrane, thus likely causing a delay in detection by immune system.
  • For viruses that replicate in the nucleus, the viral genome needs to enter the nucleus via a nuclear pore. Multiple distinct strategies are utilized, largely depending on their genome size.
  • For the virus with a smaller genome, such as polyomavirus, the viral capsid itself enters the nucleus.
  • For viruses with a larger genome, the docking of nucleocapsids to a nuclear pore complex causes a partial disruption of the capsid (eg, adenovirus) or induces a minimal change in the viral capsid (eg, herpes virus), allowing the transit of DNA genome into the nucleus.