Virus entry at a glance

Yohei Yamauchi, Ari Helenius

Research output: Contribution to journalArticle (Academic Journal)peer-review

187 Citations (Scopus)
365 Downloads (Pure)


The goal of a virus particle is to transport its genome in a replication-competent form from an infected cell to an uninfected cell. To enter a new host cell, the majority of viruses take advantage of the endocytic mechanisms of the cell and wait until reaching endocytic vacuoles or other cytoplasmic compartments before penetrating into the cytosol. After penetration, viruses and viral capsids exploit the cytoplasmic transport systems of the cell, moving to sites of replication within the cytosol (most RNA viruses) or the nucleus (most DNA viruses). The final step in the entry process generally involves uncoating of the viral genome.

After numerous entry studies with a variety of viruses in different cell systems, the overall picture of entry of animal virus into the host cell is becoming increasingly complete. There are essentially six locations for penetration. These are: (1) the plasma membrane, (2) the early endosome, (3) the maturing endosome, (4) the late endosome, (5) the macropinosome and (6) the endoplasmic reticulum (ER). Endolysosomes, amphisomes and lysosomes also remain possible penetration sites, but evidence is lacking. Some viruses can use more than one pathway, for example, by engaging different receptors.

Although the molecular details of virus–cell surface interactions are complex and highly variable, the number of pathways that allow the viruses to reach their sites of penetration seem to be limited to a handful of endocytic mechanisms. The subsequent trafficking steps involve key organelles in the endocytic network that are utilized by endogenous cargo. Only a few viruses seem to be capable of penetrating directly through the cell surface by fusing their envelope with the plasma membrane. Thus, the ‘trail map’ that is available to incoming viruses is complex, but far from incomprehensible.

In this Cell Science at a Glance article, we describe the stepwise entry program of animal viruses of different families. As illustrated in the poster, the process can be broken down into five discrete steps – attachment, signaling, endocytosis, penetration and uncoating. A more detailed description can be found in previous reviews (Damm and Pelkmans, 2006; Greber, 2002; Grove and Marsh, 2011; Gruenberg, 2009; Marsh and Helenius, 2006; Mercer and Helenius, 2009; Mercer et al., 2010; Schelhaas, 2010; Sieczkarski and Whittaker, 2002).
Original languageEnglish
Pages (from-to)1289-1295
Number of pages7
JournalJournal of Cell Science
Issue number6
Publication statusPublished - 15 Mar 2013


  • Animals
  • DNA, Viral
  • Endocytosis
  • Endosomes
  • Humans
  • RNA, Viral
  • Virus Attachment
  • Virus Internalization
  • Virus Release
  • Virus Replication
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review


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