Principles of Virology. Jane Flint

of viral capsid proteins are ~20 to 100 kDa.Explain how large icosahedral capsids can be assembled and how they differ from small capsidsWhat feature(s), other than genetic economy, dictates that all capsids are built from only a very small number of major structural proteins?

5 Attachment and Entry

        Introduction

        Attachment of Virus Particles to Cells General Principles Identification of Receptors for Virus Particles Virus-Receptor Interactions

        Entry into Cells Virus-induced Signaling via Cell Receptors Routes of Entry Membrane Fusion

        Intracellular Trafficking and Uncoating Movement of Viral and Subviral Particles within Cells Uncoating of Enveloped Virus Particles Uncoating of Nonenveloped Viruses

        Import of Viral Genomes into the Nucleus The Nuclear Pore Complex Nuclear Localization Signals Nuclear Import of RNA Genomes Nuclear Import of DNA Genomes Import of Retroviral Genomes

        Perspectives

        References

        Study Questions

      LINKS FOR CHAPTER 5

       Video: Interview with Dr. Jeffrey M. Bergelson http://bit.ly/Virology_Bergelson

       Video: Interview with Dr. Carolyn Coyne http://bit.ly/Virology_Coyne

       Bond, covalent bond http://bit.ly/Virology_Twiv210

       Breaking and entering http://bit.ly/Virology_Twiv166

       A new cell receptor for rhinovirus http://bit.ly/Virology_4-30-15

       Blocking HIV infection with two soluble cell receptors http://bit.ly/Virology_2-26-15

       Changing influenza virus neuraminidase into a receptor binding protein http://bit.ly/Virology_11-21-13

Inside this very wood hidden the Greeks are waiting, for this machine was made for our castles, to spy on our houses and quickly move against our city or maybe hiding some other deception; don't trust in the horse, Trojans.

      LAOCOÖN, VIRGIL’S THE AENEID, 29-19 B.C.E.

Introduction

      Because viruses are obligate intracellular parasites, their genome must enter a cell for the viral reproduction cycle to occur. At first sight, the physical properties of the virus particles appear as obstacles to this seemingly simple goal. Virus particles are too large to diffuse passively across the plasma membrane. Furthermore, the viral genome is encapsidated in a protective coat that shields the nucleic acid as it travels through the harsh extracellular environment. These apparent obstacles must all be overcome during the process of viral entry into cells. Infection of cells by many, but not all, viruses requires binding to a receptor molecule on the cell surface. Exceptions include virus particles of yeasts and fungi, which have no extracellular phases, and plant viruses, which are thought to enter cells in which the cell wall has been physically damaged, for example, by insects or farm machinery.

      In addition to binding viral particles, cell surface receptor molecules participate in entry, a process that relies on usurpation of normal cellular processes, such as endocytosis, membrane fusion, vesicular trafficking, and transport into the nucleus. The viral genome has to be released from the interior of the virus particle, a process known as uncoating. The receptor plays a role in this process by either initiating conformational changes that prime fusion or uncoating or by directing the virus particle into endocytic pathways, where fusion and uncoating may be triggered by low pH or by the action of proteases. These steps ultimately deliver the viral genome to the site of replication, which can be the cytoplasm, for most RNA-containing viruses, or the nucleus, for most DNA-containing viruses.

Attachment of Virus Particles to Cells

      General Principles

In animals, viral infections usually begin at the body surfaces that are exposed to the environment (Fig. 5.1; see also Volume II, Chapter 2). Epithelial cells cover these surfaces, and the region of these cells exposed to the environment is called the apical surface. Conversely, the basolateral surfaces of such cells are in contact with adjacent or underlying cells or tissues. These cells exhibit a differential (polar) distribution of proteins and lipids in the plasma membrane that creates the two distinct surface domains. Movement of macromolecules between the cells is prevented by tight junctions (Fig. 5.1).

      The first steps in virus attachment are governed largely by the probability of a random collision between a virus particle and a cell, and therefore by the concentrations of free particles and host cells. The rate of attachment can be described by the equation

      dA/dt = k[V][H]

      where A is attachment, t is time, [V] and [H] are the concentrations of virus particles and host cells, respectively, and k is a constant that defines the rate of the reaction. It can be seen from this equation that if a mixture of viruses and cells is diluted after a period sufficient for adsorption, subsequent binding of particles is reduced greatly. For example,