Lecture 9: Entry to host cells

Question 1

General entry of enveloped viruses

Answer 1

Fusion of viral envelope with host cell membrane
-Helps bring viral and cellular membranes into close proximity
-Help to ensure that fusion occurs at the correct location

Question 2

General entry of non-enveloped viruses

Answer 2

Entry into cells via endocytosis
-Genome gets across the endosomal membrane after disruption of the endosomal membrane or the formation of a pore by the virus

Question 3

Basic entry strategies & characteristics of ph-independent pathways

Answer 3

-Virus binding triggers fusion at plasma membrane
-Genome or nucleocapsid released to cytosol
-Happens at neutral pH
-NO endocytosis
-Mostly enveloped viruses

Question 4

Basic entry strategies & characteristics of pH-dependent pathways

Answer 4

-Virus binding to receptors triggers endocytosis of entire virion
-Acidic endosomal pH triggers genome release into cytosol
-Entry blocked by drugs that prevent acidification of genomes to prevent release to cytoplasm
-Used in both enveloped & non-enveloped

Question 5

Fusion peptide

Answer 5

-Exterior viral membrane polypeptide that evolve from SNARES, proteins that effect fusion of intracellular vesicles
-Interact with cytoplasm to promote fusion via a confirmation change

Question 6

Process of receptor-mediated endocytosis

Answer 6

-Ligands bind to membrane receptor proteins and migrate to clathrin coated pits
-Pit invaginates and pinches off
-Clathrin coat falls off, structure becomes a vesicle
-Vesicle fuses with early endosome and contents are transported to late endosome following acidification (Influx of protons)
-Late endosomes fuse with lysosomes when they degrade

Question 7

Acid catalyzed uncoating in influenza

Answer 7

-Virus attaches to sialic acid via a fusion protein (HA glycoprotein) and internalized via clathrin-dependent endocytosis
-In endosome, HA undergoes an acid catalyzed conformation change to expose fusion peptide to fuse membranes
-M2 ion channel pumps ions into the virion causing ribonucleoprotein to expose and leave endosome for the nucleus

Question 8

Pore formation in endosome membrane in picornaviruses

Answer 8

-Virus interacts with cell surface and i internalized by endocytosis
-PVR interaction results in conformational change of virion
-VP1 and VP4 move from inside virion to outsid and exposes hydrophobic domain to form pore in endosome
-Genome exits endosome

Question 9

Disruption of endosomal membrane in adenoviruses

Answer 9

-Endocytosis internalizes virion
-Low pH in endosome exposes penton base that lyses the endosome allowing virion to enter cytoplasm
-Virion docks with nuclear pore complex to interact with histone H1 and importins
-Capsid disassembles at nuclear pore causing DNA to be imported into nucleus

Question 10

Lysosomal uncoating in reoviruses

Answer 10

-In the endosome a very low pH triggers conformation change in lysosome
-Outer capsids shell uncoats and inner capsid is revealed
-Lysosomal vesicle is penetrated