3 The viruses Flashcards
How are major groups (families) or viruses usually classified by? 4
Type of nucleic acid
Number of nucleic acid strands and their polarity
Mode of replication
Size, structure and symmetry of virus particle
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
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
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.
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
What are host cell membrane receptor molecules for these viruses
Human parvovirus B19
Hep B
Hep C
Human rhinovirus A + B
Human rhinovirus C
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
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
Oral Droplet Direct inoculation - injection, trauma, bites Direct skin contact Sexual Transplacental
What are stages of viral infection and replication
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
How do DNA viruses produce mRNA
Can utilise host RNA polymerase
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
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)
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
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
Where does nucleic acid replication occur
Where does viral assembly occur
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
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
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
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)
HBV - HBx
EBV - LMP-1, BARF-1
HH8 - vGPCR
HPB - E6, E7
Merkel cell polyomavirus - T antigens
HTLV - Tax
What are proto-oncogenes, and what sort of thigns do they code for
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
What are 4 virion shapes
Spherical
Icosahedral
helical
Complex - bacteriophage
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?
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
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
Parvovirus B19
Group 3 dsRNA - what are examples?
Rotavirus
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
HAV HCV Rhinovirus Polio Zika
Group 5 - (-)ssRNA - what are examples
Must be converted in positive sense mRNA, before translation into proteins by host
Influenza A/B/C
Ebola
Rabies
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
HIV
HTLV
Group 7 - dsDNA what are examples
Nuclear material is circular and contains gaps due to incomplete synthesis of positive strand
HBV
What are advantages/ disadvantages of DNA genome
Larger genome - less dependent on host
DNA more stable, can repair itself
Slow replication
What are advantages/ disadvantages of RNA genome
Small genome - dependent on host
RNA unstable - mutation. e.g rapid influenza mutation during flu season to evade vaccination
Fast replication
How are viruses released from host cell? 3
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
Viruses have nucleic acid, protein capsid, and are either enveloped or non-enveloped.
What are benefits/ disadvantages of envelope?
- 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
Viruses have nucleic acid, protein capsid, and are either enveloped or non-enveloped.
What are benefits/ disadvantages of non-envelope?
- 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
Once host cell infected, what paths can host cell take?
Cell death
Persistent infection
Latent infection
EBV is an example which can do all three
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?
Failure of drug penetration to CNS
Sanctuary sites such as CNS provides different selection pressure of virus, and allow mutation to become drug resistant
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
RNA-dependent DNA polymerase - this is reverse transcriptase, used in replication cycle of HIV/ HBV
Which viruses belong to these groups -
Alpha- herpesvirinae
Beta-herpesvirinae
Gamma-herpesvirinae
Alpha- herpesvirinae
HHV1 - HSV1
HHV2 - HSV2
HHV3 - VZV
Beta-herpesvirinae
HHV5 - CMV
HHV6
HHV7
Gamma-herpesvirinae
HHV4 EBV
HHV8 KS
