1. VIRUS ENTRY

2. Virus Entry Entry Into Host Cell
Virus mission to infect as many cells as possible
Enveloped viruses utilize both fusion and endocytosis for entry making use of surface receptors
Naked viruses utilize endocytosis
Bursting and cell death occurs during release of naked viruses

4. Surface Molecules Cell Surface Receptors Facilitate Viral Entry
These receptors have other functions, simply exploited
Ex. CD4, PVR, CD46, CAR, Integrins, LDL receptor family
Carbohydrate Molecules on Lipids/Proteins Allow Viral Binding
Sialic acid is a sugar moiety that is being used by influenza and paramoxyviruses for entry
Binding has to be terminated for productive infection to occur
Neuroaminidase cleaves sialic acid in the case of influenza virus
Not Uncommon For Viruses to Use 2 Receptors
Ex. HIV, utilizes CD4 and CCR5 or CXCR4
One receptor for docking and one for endocytosis
Naked Viruses Rely on Capsid for Attachment
Ex. Adenoviruses

6. Receptor Mediated Endocytosis
We Will Refer to Clathrin Coated Pits Mechanism
Very common entry method
Via clathrin coated pits
Endocytic vesicle allow virus to move to nucleus
Low pH triggers escape from endosome
Timing is of essence since virus can end up in a lysosome and be eliminated

9. Importing Genome Into Nucleus
Advantages of Importing Genome Into Nucleus
Utilize host enzymes such as RNA polymerases, DNA polymerases and RNA processing
Disadvantage Is That Genome Has to Go Through Nuclear Pore
In Case of Retroviruses They Have to Wait For Nuclear Membrane Disintegration During Division to Occur
Lentiviruses are an exception
That is why retroviruses infect dividing cells more efficiently
Herpes Viruses and Adenoviruses Bind Nuclear Pore
They inject genome into nucleus
Capsid is too bulky to pass through pore

10. Importing Genome Into Nucleus
Some Viruses Enter Nucleus With Intact Capsid
Ex. Parvoviruses
HIV
Hep B
Influenza
Compact and economical
Picornaviruses
Unload as soon as entering host
Capsid stays at plasma membrane OR endosome
Hep B Virus
Unload as soon as entering nucleus
Intermediate Unloading: Herpes and Adeno
Capsid stays at nuclear pore

12. Ways To Block Viral Entry
Vaccination
Antibodies are generated which can block entry by binding envelope or capsid proteins
Antibody binding on capsid/envelope proteins interferes with binding on host receptors
Vaccination can be extremely effective in blocking entry
Soluble Versions of Receptors Utilized by Viruses to Enter
They bind virions and prevent binding on host receptors
Antibodies That Bind Host Receptors
These antibodies block attachment of virions onto host
Compounds That Block Acidification of Endosomes
Ammonium Chloride
Monensin (protein transport inhibitor)
Chloroquine (also used as anti-malaria drug)