Verified Answers
Downstream events following attachment of virion to its receptor - Answer Causes a
conformational change in the viral protein that enables it to bind to the co-
receptor. When the glycoprotein 120 (gp120) subunit of HIV-1 envelope binds to
the outermost immunoglobulin G domain of CD4, it undergoes a conformational
change that allows the virus to associate with its co-receptors, the chemokine
receptors CXCR4 or CCR5. The interaction between gp120 and CXCR4 or CCR5
triggers the conversion of the gp41 envelope subunit to the fusion-competent
conformation
- can also transmit signal through plasma membrane for virus uptake, penetration
and prepares cell for invasion
- also guides bound virus into a variety of endocytic pathway
Virus entry into cells - Answer Virus needs to:
- cross PM, sometimes nuclear membrane
- disassemble the virion before reaching the site of rep to make the viral genome
accessible to the cyto
- delivers nucleic acid to the correct compartment in the cells
Example of virus entry with HIV and HCV - Answer HIV: envelope engagement
with the co-receptor CXCR4 on CD4+ T cell leads to Gai signaling and subsequent
activation of actin depolymerizing protein Cofilin to induce local cortex
reorganization
HCV: crossinking EGFR and avB3 integrin resutls in cooperative activation of
PI3K and src, culminating actin reorganization
Plasma Membrane - Answer - semi-permeable in nature and results from lipid
bilayer properties and the existence of specific transport processes
- normally permeases allow transport of ions, sugars and amino acids while
proteins and large particles are taken up into the cell by phagocytosis and
endocytosis
Uptake of viruses by macromolecules into cells by phagocytosis and pinocytosis -
Answer Phagocytosis
- process by which cells engulf large particles like bacteria
Pinocytosis
, - cell drinking whereby small amounts of fluid, including dissolved
molecules/suspended small particles, are taken up by the cells and then
suspended within small vesicles
- non-specific, meaning that any particle/molecule can be taken up into the cell
Uptake of macromolecules by receptor-mediated endocytosis - Answer Receptor-
mediated endocytosis
- specific molecules are selectively taken up this way
- molecules (ligands) in the extracellular medium bind to cells via specific PM
receptor proteins
- receptor-ligand complex diffuses along the membrane until it reaches an
invagination of the PM, which is coated on its cytoplasmic surface by a cagelike
lattice, made up of the fibrous protein clathrin and is referred to as clathrin-
coated pit (CCP)
- CCP invaginates and then pinches off, forming a clathrin-coated vesicle
containing the ligand-receptor complex
- within a few sec., the clathrin coat is lost and the vesicles fuse with small
smooth-walled vesicles located near the cell surface called early endosomes
- some ligands dissociate from their receptors in the acidic environment of the
endosome and then the receptors are recycled to the cell surface by transport
vesicles that bud from the endosome and fuse with the PM
- contents of the early endosome are transported to the late endosomes located
close to the nucleus
- late endosomes fuse with lysosomes
- ligands that reach the lysosomes are degraded by enzymes for further use of
their constituents in the cell
How do viruses enter our cell? - Answer 1) Bind to surface receptors
2) Internalization of virus
3) Intracellular processing
4) Vesicular trafficking
5) Nuclear transport (viruses can hijack a nuclear protein for transport)
6) Viral replication (Transcription/replication)
Leads to uncoating (genome decondensation, disassembly/destabilization)
7) Assemble new virions
8) Exit cell since the single mission of virus particles is to transport its genome
from infected cell to non-infected host cell in a replication competent form
- require interactions with the host cell at multiple levels ranging from simple
binding to cellular receptors to complex modulation of host processes