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MICR2121 Molecular Virology > Virus Entry > Flashcards

Virus Entry Flashcards

1
Q

What are the 2 problems viruses need to solve in order to enter a cell?

A

1 - find the right cell

2 - penetrate plasma membrane to enter cell

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2
Q

What is the 3 stage process for viruses to deliver genomes into cells?

A

Attachment
Penetration
Uncoating

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3
Q

What are the 3 things involved in virus attachment?

A

Attachment factors
Virus receptors on cell surface
Cell tropism - determinant of disease causes and pathogenesis

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4
Q

What are features of virus attachment factors

A 
Glycosaminoglycans (GAGs)
Linear polysaccharides
Unlinked/linked to surface proteins
Neg charged 
bind viruses electrostatically
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5
Q

What is an example of virus receptors?

A

HRV14/16 - ICAM-1
HRV2 - LDLR

receptors have a normal function in the cell

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6
Q

How does HRV bind to the receptor?

A

receptor binding site at base of canyon

ICAM-1 can reach - antibodies cannot

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7
Q

What are HIV receptors?

A

Primary receptor - CD4 - normally binds to class II MHC on APCs

Chemokine receptors - 7TM helices - normally bind chemokines

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8
Q

What do HIV glycoproteins do?

A

multimerise to form spikes
surface protein - gp120
transmembrane protein - gp41
V3 variable tip

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9
Q

How do HIV receptor interactions occur?

A

gp 120 - neg charged GAGs on CD4

V3 loops interacts with 2nd receptor - chemokine recepro

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10
Q

How can receptors determine disease progression & pathogenesis?

A

V3 loop mutation - acidic to basic

change ability to infect certain cells

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11
Q

How can HIV infect different types of cells over time?

A

early - infect macrophages expressing CCR5

later - infect T cells expressing CxCR4

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12
Q

How can virus entry be targeted for HIV therapy?

A

Maraviroc - CCR5 antagonist - keeps virus at a low level and in the asymptomatic phase

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13
Q

What are influenza glycoproteins?

A

HA trimer gets cleaved into HA1 and HA2

HA binds to sialic acid

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14
Q

How does sialic acid linkage determines the host range of influenza?

A

Avian HA - 2,3 linkage to galactose
Human HA - 2,6 linkage to galactose

single mutation can change tropism

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15
Q

what is SARS-CoV-2 glycoproteins?

A

Spike glycoprotein trimer
cleaved into S1, S2
S1 contains receptor binding domain (RBD)

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16
Q

What is the receptor of SARS-CoV-2?

A

ACE-2
normal role in blood pressure & inflammation
cleaves angiotensin into Ang(1-9)
TMPRSS2 cleaves S protein to activate

17
Q

How do bacteriophages penetrate the bacterial cell?

A

punch hole through wall to deliver genome

18
Q

What is the cortical cytoskeleton?

A

cluster of actin and tubulin fibres - give integrity

19
Q

What are the 3 mechanisms of endocytosis?

A

1 - Clathrin mediated endocytosis
2 - Non-clathrin dependent
3 - Macropinocytosis

20
Q

What happens during clathrin mediated endocytosis?

A 
clathrin cage
membrane curvature 
pinched off vesicle 
targeted to endosomes
acidification
21
Q

What happens during non-clathrin dependent endocytosis?

A

caveolae formed from cholesterol rich lipid rafts
Targeted to ER
bunyaviruses

22
Q

What happens during macropinocytosis?

A

membrane ruffling
large vesicles
used by large viruses e.g. herpes

23
Q

How does influenza virus get into cytoplas?

A

drop to acidic pH in endosome
induces fusion of virus and membrane
capsid releases virus into cytoplasm

24
Q

How does HIV get into the cytoplasm?

A

fusion of viral and plasma membranes

release capsid into cytoplasm

25
Q

How can fusion of the virus and the membrane occur?

A

fusion peptide - short hydrophobic amino cid sequence

26
Q

What can trigger the fusion peptide to be exposed?

A
  • low pH - influenza
  • binding to co-receptor - HIV
  • after cleavage - SARS-CoV-2
  • high K+ conc - Bunyavirus
27
Q

How do intramolecular interactions force membranes together

A

fusion peptides originally hidden now stick out
interact with plasma membrane
glycoproteins contract to squeeze 2 membranes together

28
Q

What are the 3 ways a non-enveloped virus can enter the cytoplasm?

A

1 - uncoating before endosome disruption
2 - endosome disruption before uncoating
3 - pore formation

29
Q

What is virus uncoating and what triggers it?

A

exposure of genome for replication/translation

pH
Acidification

30
Q

How does mimivirus uncoat?

A

stargate opens up to release genome

31
Q

How does Influenza enter the nucleus?

A

transport of uncoated virus material

RNP complexes attch to nuclear protein

32
Q

How does HIV enter the nucleus?

A

reverse transcription with partially uncoated capsid

33
Q

How does herpes virus enter the nucleus?

A

taken along down microtubules

uncoating at nuclear pore - DNA inserted with associated proteins

MICR2121 Molecular Virology (15 decks)

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