VIRUS ENTRY Virus Entry Entry Into Host Cell

VIRUS ENTRY

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

Surface Molecules • Cell Surface Receptors Facilitate Viral Entry – These receptors have other functions, simply exploited – Ex. CD 4, PVR, CD 46, 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 CD 4 and CCR 5 or CXCR 4 • One receptor for docking and one for endocytosis • Naked Viruses Rely on Capsid for Attachment – Ex. Adenoviruses

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 p. H triggers escape from endosome – Timing is of essence since virus can end up in a lysosome and be eliminated

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

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

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) •