Attachment and entry of viruses into cells

1. LECTURE 9: Attachment and entry of viruses into cells WaqasNasirChaudhry Viro100: Virology 3 Credit hours NUST Centre of Virology & Immunology

2. Virus aim to get replicate • To achieve it, virus need to enter into the cell • In general replication of virus can be divided • Attachment of a virion to a cell • Entry into the cell • Transcription of virus genes into messenger RNA molecules (mRNAs) • Translation of virus mRNAs into virus proteins • Genome replication • Assembly of proteins and genomes into virions • Exit of the virions from the cell

3. ATTACHMENT VIRAL LIFE CYCLE HOST FUNCTIONS PENETRATION UNCOATING Transcription Translation REPLICATION ASSEMBLY (MATURATION) RELEASE MULTIPLICATION

4. Cell receptors and co-receptors • A virion attaches via one or more of its surface proteins to specific molecules on the surface of a host cell • These cellular molecules are known as receptorsand the recognition of a receptor by a virion is highly specific, like a key fitting in its lock • It has been found that some viruses need to bind to a second type of cell surface molecule (a co-receptor) in order to infect a cell.

5. HIV entry process. (a) CD4–gp120 binding, (b) gp120-co-receptor interaction and (c) viral and cellular membrane fusion

7. Receptors and co-receptors are cell surface molecules, usually glycoproteins, with a wide range of functions that include • acting as receptors for chemokines* and growth factors • mediating cell-to-cell contact and adhesion *Chemokines are a family of small proteinssecreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines

9. Virus attachment sites • Each virion has multiple sites that can bind to receptors, and each site is made up of regions of one or more protein molecules • The virus attachment sites of some naked viruses are on specialized structures, such as the fibresand knobs of adenoviruses • while the virus attachment sites of enveloped viruses are on the surface glycoproteins

10. Adenovirus virion Enveloped Viruses

11. Some virion surface proteins that bear the virus attachment sites are able to bind strongly to red blood cells of various species • Cause them to clump, a phenomenon known as haemagglutination • The proteins responsible for aemagglutination are called haemagglutinins • Examples are influenza viruses and measles virus

12. Haemagglutination

13. Evidence that a cell surface moleculeis a virus receptor • Block the cell surface with antibodies • Soluble derivatives of the molecule block virus binding/infectivity • The normal ligand for the molecule blocks virus binding/infectivity • Introduction of the gene encoding the molecule into virus resistant cells, and expression of that gene, makes those cells susceptible to infection

14. Block the cell surface molecule with antibodies

15. Soluble derivatives of the molecule block virus binding/infectivity

17. Human Rhino Virus

18. Polio Vp1 interacting with CD155p1

19. Influenza Virus Receptor

20. Influenza Virus Receptor Sialic acid is always the last sugar in a chain that is attached to a protein. On the right is the chemical structure of sialic acid; the next sugar, to the right, is galactose. Influenza virions attach to cells when the HA grabs onto the very small sialic acid.