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Miguel > Barriers To Viral Infection > Flashcards

Barriers To Viral Infection Flashcards

1
Q

Generalised virus replication cycle

A

Attachment/uncoating
Transcription
Translation
Replication
Assembly
Release

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2
Q

Barriers to viral infection (4)

A

Immunological
Biochemical
Physical
Genetic

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3
Q

Geographical barriers

A

Location

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4
Q

Biological barriers (6)

A

Skin
Mucous membranes
Mucous
Tears
Stomach acid
Intestinal secretions

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5
Q

Dengue virus

A

An example of a geographical barrier
Transmitted by mosquitos, transmission limited by mosquito distribution

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6
Q

Coxackie/adenovirus receptor (CAR)

A

CAR not found on apical surface, so virus has to find the receptor deep in the cell

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7
Q

Viral precursor protein cleavage

A

Paramyxovirus F protein
Influence virus HA

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8
Q

HIV receptors

A

CD4
CCR5 or CXCR4
Found on human T cells

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9
Q

Avian sarcoma and leukosis virus receptors

A

TVA
TVB

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10
Q

Paramyxovirus fusion protein cleavage is…

A

Required for function

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11
Q

RSV paramyxovirus F protein cleavage

A

Furin enzyme
Trans golgi
Systemic

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12
Q

SeV paramyxovirus F protein cleavage

A

Tryptase clara
Extracellular
Respiratory tract

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13
Q

RSV F fusogenic activity is measured by

A

Fusion assay w/o acetylated trypsin
LLC-MK2 cells
Incubate SeV WT = weak fusogenic activity
Incubate SeV/RSV F = strong fusogenic activity

Incubation is 5-6 days at 33oC

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14
Q

_____ cleavage is essential for virus infectivity.

A

HA

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15
Q

Genetic barriers to infection (2)

A

Retroviruses - > APOBEC3G
SARS-CoV-2 - > ACE2

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16
Q

Retrovirus Vif

A

Blocks APOBEC3G activity

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17
Q

APOBEC3G

A

Packaged into virions
Hypermutation of minus strand cDNA (dC to dU)
Defective non-infectious progeny

18
Q

HIV Vif blocks ________ APOBEC3G

A

Human and green African monkey

19
Q

SIV Vif blocks __________ APOBEC3G

A

Simian

20
Q

Immunological barriers

A

Type 1 interferon
Antigen presentation

21
Q

IFN induction 2nd wave

A

Newly synthesized IFN-β, from the first wave, binds to the type I IFN receptor and activates the expression of numerous ISGs via the JAK/STAT pathway.

IRF-7 amplifies the IFN response by inducing the expression of several IFN-β subtypes. SOCS and PIAS are negative regulators of the JAK-STAT pathway. Mx, ISG20, OAS and PKR are examples of proteins with antiviral activity.

22
Q

dsRNA, a characteristic by-product of virus replication, leads to activation of…

A

the transcription factors NF-κB, IRF-3 and AP-1

23
Q

How is IFN-Beta promoter activated?

A

Cooperative action of NF-κB, IRF-3 and AP-1

24
Q

What is the second signalling pathway for formation of TBK-1/IKKe?

A

A second signaling pathway involves endosomal TLR-3 and TRIF.

25
Q

Interferon signalling pathways

A

Type I IFNs bind type I IFN receptor, composed of two subunits, IFNAR1 and IFNAR2, which are associated with TYK2 and JAK1

Type II IFN, IFN-γ, binds type II IFN receptor, composed of two subunits, IFNGR1 and IFNGR2, which are associated with JAK1 and JAK2, respectively.

Activation of JAKs associated with type I IFN receptor => tyrosine phosphorylation of STAT2 and STAT1=> ISGF3 complexes=> bind IFN-stimulated response elements in DNA => gene transcription.

Both type I and type II IFNs also induce the formation of STAT1–STAT1 homodimers that translocate to the nucleus and bind GAS (IFN-γ-activated site) elements that are present in the promoter of certain ISGs, thereby initiating the transcription of these genes.

26
Q

Rubulavirus V proteins (C-ter) inhibition of interferon signalling

A

STATs to proteasome

27
Q

Respirovirus C proteins (C-ter) inhibition of interferon signalling

A

Inhibit STAT1, STAT2 or TYK2 tyrosine phosphorylation

28
Q

Morbillivirus V proteins (C-ter) inhibition of interferon signalling

A

Inhibit STAT1, STAT2 tyrosine phosphorylation
STAT1/IFNr complex retained

29
Q

Henipavirus P,V, W (N-ter) inhibition of interferon signalling

A

STATs sequestered in high molecular weight complexes

30
Q

Pneumovirus NS1 and NS2

A

STAT2 to proteasome

31
Q

Sendai Virus C protein inhibiting interferon role in pathogenicity

A

WT => blocks STAT1 signalling = anti-IFN activity
Cm* mutant (3 amino acid substitutions) = > no anti-IFN activity

32
Q

Type 1 IFN system in virus induction and suppression

A

Major player in antiviral defence
Secreted in response to viral infection
Induce expression of potent antiviral mechanisms

Virus ability to block type I IFN system determines …
Virulence
Interspecies transmission

33
Q

HIV nef protein

A

Down regulates MHC expression on infected cells
Redistributes CD80 and CD86 away from cell surface in antigen presenting cells
- functionally significant
- compromises activation of naive T cells

34
Q

Mucosal epithelium

A

Mucus layer
Cilia
Goblet Cells
Glycocalyx -> thick layer over endothelial cells

35
Q

MeV paramyxovirus F protein cleavage

A

Furin
Trans-Golgi
Systemic

36
Q

HA cleaved by __________

A

Host protease
Eg furin

37
Q

What reverses the species specificity in APOBEC3G?

A

Single amino acid change

38
Q

Type I IFN system?

A

Virus binds to first cell and releases ds RNA
Signalling cascade - TNF beta
TNF beta released from cell and binds to interferon receptor of neighbouring cell

39
Q

Berlin patient

A

HIV 1 + leukaemia
Bone marrow transplant to treat leukaemia
Transplant with new donor marrow which happened to have CCR5 mutation only in 10% of population mainly Europeans
-> cured of HIV

40
Q

Biochemical barriers

A

Viral receptors
Viral precursor protein cleavage

Miguel (8 decks)

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