3 The viruses Flashcards

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1
Q

How are major groups (families) or viruses usually classified by? 4

A

Type of nucleic acid
Number of nucleic acid strands and their polarity
Mode of replication
Size, structure and symmetry of virus particle

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2
Q

Viruses range from parvovirus (parvo means small) 18-26nm diameter, to quite large vaccinia virus 400nm, which is as big as some bacteria.

What is general structure which viruses have in common

A

Genetic material either
single or double stranded
Linear or ciruclar
RNA or DNA (never both)

Complete unit of nucleic acid and capsid is called nucleocapsid. This often has distinctive symmetry depending on arrangement of capsomeres.

Nucleocapsid can be surrounded by outer lipid envelope, usually comes from host cell, and has virus glycoproteins inserted into it. This new organism is called a virion

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3
Q

What are host cell membrane receptor molecules for these viruses

Influenza

Rabies

HIV

EBV

Viruses show host specificity and usually only infect one species, and one type of cell.

A

Influenza - haemagluttinin binds to sialic acid (glycoprotein) receptor on respiratory epithelial cells

Rabies - acetylcholine receptor, neuronal cell adhesion molecule

HIV - CCR5/ CXCR4

EBV - CD21 receptor on B cells

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4
Q

What are host cell membrane receptor molecules for these viruses

Human parvovirus B19

Hep B

Hep C

Human rhinovirus A + B

Human rhinovirus C

A

Human parvovirus B19 - P antigen on erythroid progenitor cells

HepB - Sodium taurocholate - hepatocytes

Hep C - CD81 hepatocytes

Human rhinovirus A + B - ICAM-1 respiratory epithelium

Human rhinovirus C - CDHR3 respiratory epithelium

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5
Q

Structure of outer surface of virion is important as this is what first makes contact with host. Viruses have to be resistant and survive in outside world - e.g bile and gastric acid resistant, environmental drying/ heat. These susceptibilities influence ways in which these viruses can be transmitted,

What are routes by which viruses enter body

A
Oral
Droplet
Direct inoculation - injection, trauma, bites
Direct skin contact
Sexual
Transplacental
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6
Q

What are stages of viral infection and replication

A

Attachment - receptor binds to host membrane

Penetration

Uncoating - capsid shed. Virus no longer infective - termed eclipse period

Replication - synthesis of viral RNA (direct or via host machinery), synthesis of viral protein/ capsid

Assembly - capsid forms around nucleic acid

Release - either by budding forming envelope or cytolysis - no envelope

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7
Q

How do DNA viruses produce mRNA

A

Can utilise host RNA polymerase

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8
Q

RNA viruses must supply their own enzymes to produce mRNA

How to these configurations produce mRNA -

dsRNA

single strand positive sense

single strand negative sense

retroviruses

A

dsRNA - one strand first transcribed by viral polymerase into mRNA

single strand positive sense (same base sequence required for translation) - it can be used directly as mRNA

single strand negative sense - must be transcribed using viral polymerase into positive sense strand, which can then act as mRNA

retroviruses have positive sesnse ssRNA.
Converted into DNA using viral reverse transcriptase
Integrase inserted into host genome - provirus. mRNA created as normal using human RNA polymerase

(HIV, HTLV and HBV are only viruses infecting humands that have reverse transcriptase ability)

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9
Q

Viral mRNA is translated in host cytoplasm viral proteins
Ribosomes used to sythesise viral proteins. Viral mRNA can displace host mRNA, and take preference for translation. In early phase enzymes are translated first, then proteins for capsid formation. mRNA can also code for massive polypeptide, which is then cleaved enzymatically into smaller proteins.

Nucleic acid also needs to be replicated.

How to these viruses replicate nucleic acid -

positive sense ssRNA

negative sense ssRNA

dsRNA

A

positive sense ssRNA translated into negative sense mRNA. This acts as template, and repeatedly transcribed into more positive strands ssRNA

negative sense ssRNA transcription by viral polymerase produces positive sense RNA strands, from which new negative sense RNA is produced

dsRNA - positive sense RNA strands produced. These act as templates in a subviral particle for synthesis of new negative sense strands to restore the double-stranded condition

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10
Q

Where does nucleic acid replication occur

Where does viral assembly occur

A

In host nucleus, except poxvirus where it takes place in cytoplasm

Assembly involves association of nucleic acid and capsomeres to form nucleocapsid. Takes place in cytoplasm usually, can be nucleus. Viral glycoproteins insert into host membrane, so when virus buds it takes cell membrane, glycoproteins such as neuramindase

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11
Q

Some viruses (usually persistent) can transform host cell into tumour, by causing change in morphology, behaviour and biochemistry (oncogenic virus). Controlled growth patterns are lost, so cells can grow randomly.

Can be cancerous or non cancerous - e.g papillomavirus can cause cervical cancer, or cause warts on hand

Name specific viruses which are oncogenic 7 -

  • Those which integrate host DNA
  • Those that do not integrate
A

HBV
HTLV
Papillomavirus - cervical/ anal/ oropharyngeal carcinoma
Merkel cell virus - rare skin cancer

HCV
EBV - first one discovered 1964 Burkitt’s lymphoma/ nasopharyngeal carcinoma
HHV8

HIV does not cause caause cancer directly, but can lead to EBV and HHV8 (Kaposi sarcoma) infection

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12
Q

Whcih oncogene is activated by each virus

HBV

EBV

HH8

HPB

Merkel cell polyomavirus

HTLV

Oncogenes have short acronyms e.g v-myc means viral oncogene origin, and c-myc for cellular origin. Viruses which insert into genome can integrate near oncogene (causing upregulation), or near tumour suppressor genes (causing down regulation)

A

HBV - HBx

EBV - LMP-1, BARF-1

HH8 - vGPCR

HPB - E6, E7

Merkel cell polyomavirus - T antigens

HTLV - Tax

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13
Q

What are proto-oncogenes, and what sort of thigns do they code for

A

Cellular oncogenes

Role is host cell growth regulation -

  • may code for growth factors
  • receptor molecules which bind to growth factors
  • components of intracellular signalling systems
  • DNA binding proteins that act as transcription factors
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14
Q

What are 4 virion shapes

A

Spherical
Icosahedral
helical
Complex - bacteriophage

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15
Q

Viruses are grouped in 7 groups according to nucelic acid, termed Baltimore classification.

All viruses must direct the synthesis of mRNA to produce proteins. No viral genome encodes a complete system for translating proteins; therefore all viral protein synthesis is completely dependent upon the translational machinery of the cell. Baltimore created his virus classification scheme based on the central role of the translational machinery and the importance of viral mRNAs in programming viral protein synthesis.

By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis. A strand of DNA of the equivalent sequence is also called the (+) strand. RNA and DNA strands that are complementary to the (+) strand are, of course, called negative (-) strands

Group 1 - dsDNA - what are examples?

A
Group 1 - dsDNA -
Herpes virus
Pox virus
Human adenovirus
Human polyomavirus
Human papillomavirus

Viral DNA transported to host nucleus for transcription and translation, but remaisn separate from host DNA

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16
Q

Group - 2 (+)ssDNA - what are examples?

Host cells can’t use single stranded DNA for replication or transcription. Brings it’s own proteins to convert to dsDNA

A

Parvovirus B19

17
Q

Group 3 dsRNA - what are examples?

A

Rotavirus

18
Q

Group - 4 (+)ssRNA - what are examples?

Positive sense can remain in host cytoplasm and acts directly as mRNA and translated into proteins.
Requires RNA polymerase to replicate genome

A
HAV
HCV
Rhinovirus
Polio
Zika
19
Q

Group 5 - (-)ssRNA - what are examples

Must be converted in positive sense mRNA, before translation into proteins by host

A

Influenza A/B/C
Ebola
Rabies

20
Q

Group 6 - (+)ssRNA retroviruses

Different to Group 4 (+)ssRNA.
Group 6 use reverse transcriptase to convert to dsDNA, and integrase to insert into host DNA

A

HIV

HTLV

21
Q

Group 7 - dsDNA what are examples

Nuclear material is circular and contains gaps due to incomplete synthesis of positive strand

A

HBV

22
Q

What are advantages/ disadvantages of DNA genome

A

Larger genome - less dependent on host

DNA more stable, can repair itself

Slow replication

23
Q

What are advantages/ disadvantages of RNA genome

A

Small genome - dependent on host

RNA unstable - mutation. e.g rapid influenza mutation during flu season to evade vaccination

Fast replication

24
Q

How are viruses released from host cell? 3

A

Exocytosis - leave fully formed

Budding - virion glycoproteins from on host membrane, and when virion buds off, takes glycoproteins as lipid envelope

Cell lysis - host cell membrane interfered with, and cell inevitably dies, virus released

25
Q

Viruses have nucleic acid, protein capsid, and are either enveloped or non-enveloped.

What are benefits/ disadvantages of envelope?

A
  • Difficult target for host immune system, as envelope formed from host proteins
  • No cell lysis required
  • Sensitive to extreme pH - does not enter via GI tract
  • Sensitive to heat, dryness, and simple disinfectants
26
Q

Viruses have nucleic acid, protein capsid, and are either enveloped or non-enveloped.

What are benefits/ disadvantages of non-envelope?

A
  • Less sensitive to extreme pH - can enter via GI tract
  • Less sensitive to heat, dryness, and simple disinfectants
  • Easier target for host immune response
  • Causes cell lysis which is highly immunogenic event
27
Q

Once host cell infected, what paths can host cell take?

A

Cell death

Persistent infection

Latent infection

EBV is an example which can do all three

28
Q

HIV on long term ART, presents with new onset confusion.

Viral load in plasma - undetectable
Viral load in CSF - 4.7 log10 copies/ml

What explains likely difference between plasma and CSF?

A

Failure of drug penetration to CNS

Sanctuary sites such as CNS provides different selection pressure of virus, and allow mutation to become drug resistant

29
Q

Patient co-infected HIV and HBV started on tenofovir and emtrictabine (Truvada)

What is target of this drug combination?

Cellular RNA polymerase II
DNA-dependent DNA polymerase
DNA-dependent RNA polymerase
RNA-dependent DNA polymerase
RNA-dependent RNA polymerase
A

RNA-dependent DNA polymerase - this is reverse transcriptase, used in replication cycle of HIV/ HBV

30
Q

Which viruses belong to these groups -

Alpha- herpesvirinae

Beta-herpesvirinae

Gamma-herpesvirinae

A

Alpha- herpesvirinae
HHV1 - HSV1
HHV2 - HSV2
HHV3 - VZV

Beta-herpesvirinae
HHV5 - CMV
HHV6
HHV7

Gamma-herpesvirinae
HHV4 EBV
HHV8 KS