VPI Biology and Physiology 2 Flashcards

1
Q

How does HIV onvercome the small nucleic acid load in capsid…?

A

1) Multiple ‘reading frames’ allows virus to transcribe same DNA into different protein seq,

Use of Polyproteins (large precurosers that are cleaved to form functional smaller proteins)

Use of single Capsid protein
(p24 capsid protein hex,dim,pentamers)

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2
Q

How does the use of polyproteins save genetic space

A

Allows for more compact genome by eliminating ( genetic features e,g promoters)

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3
Q

HIV has 3 genes Encoding polyproteins

A

1) ENV gp-120 and gp41 (attachment and fusion (release))
2) POL ( Reverse transcriptase)
3) GAG ( Capsid & matrix proteins)

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4
Q

HIV-1 Tropism

A

HIV enters cells via cellular receptor and co-receptor

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5
Q

Co receptors on:

i) macrophages
ii) T-lymphocytes

A

i) CCR5

ii) CXCR4

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6
Q

Early HIV and Late HIV

A

Early hiv infects macrophages (CCR5) during later infection it infects CD4+ T-lymphocytes (CXCR4)

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7
Q

Rapid progression to AIDS is associated with..?

A

With the switch in HIV-1 Tropism from macrophages to CD4+T cells

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8
Q

HIV Entry : attachment

A

Gp120 Binds to CD4 on host cell

Conformational change in gp120 allows interaction with co-receptor CCR5 or CXCR4

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9
Q

Hiv entry 2: Fusion

A

Further conformational changes results in gp41 Fusogenic tip insertion into cell -> Fusion of viral and cellular membranes

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10
Q

Enfuvirtide : Fusion inhibitor : MOA

A

Inhibits fusion process preventing virus from infecting cell

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11
Q

HIV-1 Entry inhibitors (3)

A

1) gp120-CD4 binding
2) gp120-coreceptor binding
3) gp41-mediated membrane fusion

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12
Q

Natural resistance to HIV infection

A

CCR5 not being displayed (resistance)

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13
Q

HIV uncoating after uptake (2 developmental stages are…?)

A

Reverse transcription compelx (RTC)

Pre-intergration complex (PIC)

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14
Q

Retroviral RT: 3 biochemical activiteis

A

RNA-dependent DNA polyermase

RNAse H (nuclease)

DNA-dependet DNA polymerase activity

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15
Q

What occurs in the retroviral Reverse transcripatase activiteis?

A

1) RT of RNA -> DNA
2) RNA is cleaved and degraded
3) use First strand DNA to complete (then intergrate into host genome)

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16
Q

Reverse transcriptase (RT) inhibitors example

A

zidovudine

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17
Q

Intergration of HIV viral DNA

A

Done by Intergrase (encoded by viral pol gene)

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18
Q

Intergrase inhibitors e.g and MOA:

A

Raltegravir

Targets intergrase viral DNA in the PIC

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19
Q

Replication occurs via

A

When DNA is copied viral DNA is copied aswell.

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20
Q

Assembly Budding and Maturation;

What does GAG encode..?

A

GAG gene encodes Structural proteins of the viral caspid (needs to be cleaved from polyprotein)

Cleavage of HIV results release of matrix proteins (MA, CA, NC, p6)

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21
Q

What are MA, CA, NC and p6?

And viruses that have not undergone full maturation by….. are ….?

A

MA - Matrix protein
CA - Capsid protein
NC - Nucleocapsid
p6 - intiates budding

Full maturation by proteolytic cleavage (HIV protease) are not infective

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22
Q

Protease inhibitors :

A

Bind and block the active site of HIV protease

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23
Q

All the classes of drugs against HIV infection;

A

Entry Inhibitors
Reverse transcriptase inhibitors
Intergration inhibitors
Protease Inhibitors

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24
Q
Examples of each class of drug;
Entry inhbitors
RT inhibitors
Intergration inhibitors
HIV protease inhibitors
A

1) Maraviroc
2) Zidovudine
3) Raltegravir
4) Saquinavir

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25
Q

Cold and flu: Transmission

A

Airbone droplets
Fomites
Hand-to-hand contact
hand-to-suraface-to-hand contact

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26
Q

Influenza :

A

Large enveloped (-)ssRNA (B group V) virus

Rhinovirus small non-enveloped

Adenovirus large (non-enveleoped)

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27
Q

Influenza A : infects

A

Humans, horses pigs

28
Q

Influenza Virus: Features

A

Characteristic spikes
Haemagglutitin (HA)
Neruaminidase (NA)
(-) ssRNA

29
Q

Influenze Virus : Structure

A
Matrix protein (M1)
Lipid bilayer (envelope)
HA (Trimer)
NA ( Tetramer)
Ion channel (M2)
30
Q

Influenza Virus: Genome structure:

A

8 Seperate (-)ssRNA molecules

31
Q

Influenza A: Subtypes

And combinations..?

A

Subtypes based on HA and NA proteins on their surface

Can occur in all combinations
H(1-16) N(1-9)

32
Q

Influenza A subtypes are distinguishable …..?

A

Influenza A subtypes are distinguishable seriologically

33
Q

Zoonotic influenza strains

A
Swine Flu (H1N1)
Avian Flu (H5N1)
34
Q

Influenza : Attachment and Entry

A

HA protein (trimer) mediates attachement to Silaic acid on cell surface

-> Uptake into endosomes

35
Q

Sialic acid: Structure

A

Sialic acid is a transmembrane glycoprotein carrying terminal sialic acid

Acts as attachment site influenza virus

Sialic acid attached to a galactose molecule in a(2,3)

36
Q

Neuriminidase (NA) cleaves at which bond?

A

NA (Tetramer) cleaves at the O-C bond between Sialic acid and Galactose
(VIRAL RELEASE)

37
Q

Influenza viruses: Selectivity

A

Human influenza bind to a-2,6

Avian influenza bind a2,3

38
Q

Zoonotic Influenza : genetic exchange : How does it happen?

A

Avian flu given to pig ( as they have both a-2,3 and a-2,6 linkage)
Then genetic exchange (reassorement) can create new strains
-> now influenza binds to both glycosidic linkages -> Infect humans

39
Q

Pandemics are caused by

A

Antigenic shift due to genetic exchange (reassortment)

40
Q

Influenza virus: uptake/release in endosomes

A

Endosome contains a proton pump which decrease endosmal ph to ~5

M2 Ion channel channels protons into virion Lowering
pH

RESULTS in fusion of viral envelope with endosomal membrane and release 8(-)ssRNA

41
Q

Influenza Virus: Fusion

A

HA mediates fusion of viral envelope with endosomal membrane

Lower pH induces rearrangment of protein

42
Q

M2 Ion channel Blocker : Amantadine

A

Blocks the M2 ion channel
Stopping pumping protons into endosomal vesicle ->

interferes with release and HA mediated fusion viral envelope and endosomal membrane

43
Q

Neuramindiase (NA) inhibitors + example

A

Mimic the NA natural ligand sialic acid (block viral escape from infected cells)

E.g Tamiflu

44
Q

Rhinovirus: receptor

A

ICAM LDLR

45
Q

Adenovirus receptor :

A

CAR and CD46

46
Q

Hepatitis is ….?

A

The inflammation of the liver (leads to cirrhosis)

47
Q

Liver cirrhosis is characterised by:

A
  • Fibrosis (liver tissue replaced with collagen)
  • Regenerative nodules (attempt to repair)

(Irreverisble)

48
Q

Hepatisis :

i) Naked DNA
ii) enveloped DNA

A

i) Hep A and E

ii) Hep B,C,D

49
Q

Diffences in infection from

i) Naked DNA Hep
ii) Enveloped DNA Hep

A

i) Cause acute infections

ii) Cause chronic and persistnet infections

50
Q

Hepatitis : Symptoms

A

Jaundice or Icterus (yellow)

51
Q

What is Jaundice caused by…?

A

Jaundice is caused by the buildup of bilirubin in the blood

Usually cleared by in healthy liver

52
Q

Hepatitis virus; Modes of transmission

i) Naked
ii) Enveloped

A

i) Faecal-oral Route

ii) Blood-to-blood contact & sexual

53
Q

Hepatitis A virus: HAV

A

Acute

Induces lifelong protection against reinfection

54
Q

HAV structure:

A

Non-eveloped covered by capsid

Capsid made of 3 polypeptides (VP1 -> VP3)

55
Q

HBV : Key facts

A

25% individuals with HBV get cirrhosis , 10% get liver cancer

56
Q

HBV : Structure

A

Enveloped, uses RT

57
Q

HCV: Key facts

A

No vaccine

Asymptomatic until late stages

58
Q

HEP C structure:

A

Enveloped, E1 & E2 and capsid

59
Q

HEP C : Treatment

A

Drug : Ribavirin
(pegylated -> more stabling longer circulation)
Ribavirin is tertogenic & Genotype 1 harder to treat (1/3)

60
Q

HDV : Key facts

A

Is defective virus

Requires Co-infection with HBV (Providing antigents need for attachment and infection)

61
Q

HDV May lead to…..

A

HDV leads to hepatocellular carcinoma

62
Q

Passive Vs Active immunisation…?

A

Passive - Injection of pathogen-specfic immunoglobulins (antibodies)

Passive -> no long term protection (good post exposure)

Active -> Long term

63
Q

Types of Vaccines

A

Live Attenuated Vacines
Inactivated Vaccines
Subunit Vaccines

64
Q

Live attenuated vacciness :

A

Viruses grown in cultures and viruses with LOW VIRULENCE selceted (Immune response close to natural)

65
Q

Inactivated Vaccines

A

Viruses inactivaed and few side effects (immune response weaker)

66
Q

Sub-unit vaccines

A

Surface antigents produced by recombinant DNA technologies
(No pathogen present)
Immune respone weaker

67
Q

Vaccinations are avaible for …?

A

HAV & HBV