L1- VIRAL DIVERSITY

Question 1

what is a virus

Answer 1

• a small non-cellular agent, consisting largely of nucleic acid within a protein coat, requiring a host cell for reproduction
• generally, not considered to be alive (with less and less confidence as more viruses are discovered to be similar to live forms – ex. Pandora virus: large structure, large genome, lack of capsid)

Question 2

Classification of viruses based on:

Answer 2

1. Genome diversity:
   * DNA or RNA
   * double-stranded or single stranded
   * circular or linear
   * +sense or –sense
   * segmented or non-segmented
   different genomes require different replication strategies and hence life cycles
2. Morphological diversity
   * size: range from 30 nm in diameter to ~1 micron
   * viruses are usually too small to be viewed by light microscopes (use EM)
3. Host specificity

Question 3

DNA vs RNA

Answer 3

• DNA viruses have a larger range of genome size then RNA viruses
• Max genome size of RNA viruses ~20 kb due to RNA polymerases lack of proof-reading activity – if the genome gets too large, RNA pol will generate a lot of mutations, resulting in defective progeny variants, so they are unable to produce replication confident progeny variants
• Exception: Nidoviruses ex. SARS-COV-2 – allowed to have a larger genome size (up to 42 kb) because they have extra genes that encode for a separate protein that perform the proofreading RNA polymerase activity
• Viruses with small genomes often have overlapping genes to maintain their small size
  o DNA,RNA have 3 ORF due to codons being read in triplet
  o Some reading frames may overlap
  o Therefore, the same region of RNA can encode for more than 1 proteins
  o Ex. HIV genomes are only ~ 9 kb but encode for a lot of proteins

Question 4

double-stranded or single stranded

Answer 4

• most RNA viruses are single-stranded
  o exceptions are reoviruses (not retrovirus)
• most DNA viruses are double-stranded
  o exceptions are some small viruses (less than 4000bp) such as parvoviruses

Question 5

circular or linear

Answer 5

• most viruses are linear, but some have circular genomes
• most have a particular type of repeats at the ends of the linear DNA to help with replication
• ex. of circular genome virus: SV40 (dsDNA)
  o undergoes rolling circle replication
  o a monkey virus discovered in vaccine cell lines for polio
  o infection causes cancer in rodent cells due to SV40 abortive infection, causing cell transformation. In human cells, SV40 just replicates and does not cause abortive infection, thus no cell transformation and does not cause cancer in humans.

Question 6

-sense or +sense

Answer 6

• • sense: A type of single stranded RNA virus whose genetic material is the viral 5’-3’ mRNA that encodes for proteins and can be readily translated.
• – sense: A type of single stranded RNA virus whose genetic material is the antisense strand (3’ to 5’) of the viral mRNA. Therefore, it requires RNA polymerase for the transcription into + sense viral mRNA first before translation into protein.

Question 7

segmented or non-segmented

Answer 7

• monopartite: have 1 single nucleic acid molecule (genome is not segmented)
  o monopartite viruses evolve by mutation and recombination (co-infection of the same host cell by 2 different viruses results in RNA pol switching between the 2 viral genome templates during the replication stage, producing chimeric re-combined viruses)
• multipartite: genome is divided into 2 or more nucleic acid segments
  o ex. Influenza (-ve sense virus w/ segmented RNA genomes)
  o multipartite viruses evolve by mutation, recombination, AND reassortment (co-infection of the same host cell by 2 different viruses results in random packaging of both viruses’ genomic segments)
   often occurs in a mixing vessel ex. pigs get infected by both avian H3 virus and humans H2 virus, causing reassortment in pigs which gives rise to H3 virus variant that can go on to infect humans
   often lead to pandemics
• Large DNA viruses are often linear & monopartite while RNA viruses are often multipartite

Question 8

simplest virion particles

Answer 8

• simplest virion particles have a genome surrounded by a capsid (coat) which protects the nucleic acid and/or allow viruses to bind to receptors on cell surfaces
  o ex. TMV (+sense single-stranded RNA genome + capsid monomer)

o the virion particle itself does not contain any polymerase protein/ other viral proteins. Those are encoded in the viral genome.

Question 9

how do virion structures assemble

Answer 9

• Virion structures assemble spontaneously – if viral RNA and capsid proteins are combined in a test tube, will get infectious viral particles
  o Viral RNAs have packaging signal in their sequence which will bind the capsid protein as they assemble
  o Regular shapes of capsid proteins can assemble into any icosahedral conformations (have icosahedral symmetry)

Question 10

parts of virion structure

Answer 10

• some viruses can have an envelope in addition to a capsid ex. filovirus (ebola) - highly infectious (need only a few/1 viral particle to cause the disease) but not contagious (can be passed on easily) vs. polio (not infectious but highly contagious)
  o envelope = a lipid membrane derived from host cells in a process called “budding off.” During the budding process, newly formed virus particles become “enveloped” or wrapped in an outer coat that is made from a small piece of the host cell’s plasma membrane.
  o viral envelopes are embedded with envelope proteins which are usually glycosylated and are responsible for binding to host cells
• can consist of matrix: protein that stabilizes the whole viral particle – cross links the internal core regions (capsid) to the external membrane
• their capsid can also be differentiated (consist of several proteins)

Question 11

Host specificity

Answer 11

• some viruses are host specific – can only infect 1 reservoir species (the virus’ direct natural target)
  o ex. smallpox, polio, measles are human specific (good target for eradication – no reinfection from animal reservoirs)
• some viruses have more than 1 host, thus can infect more than 1 reservoir species & can transmit directly from 1 reservoir species to another
• humans may or may not be natural targets/ reservoir of these viruses
• some viruses can have vectors - natural reservoirs that can pass the infection on to other non-natural targets

Question 12

examples of viruses with vectors

Answer 12

o ex. mosquitos and arthropods are good vectors which will pass on the virus to other animals by biting (can cross the skin barrier)
o some species they pass on to can be dead end carriers – can’t pass the virus on to other organisms in the same species or any other species including back to the vector – but they can still be affected (get ill)
o therefore, many viruses can cause zoonosis - an infection or disease that is transmissible from animals to humans (or humans to animals) under natural conditions (ex. rabies)

Question 13

discovering new viral disease in humans

Answer 13

• if discover a new viral disease in humans, need to find reservoir host effectively
  o trap any local animals in the areas of outbreak to observe the presence of any viruses
  o first look at the mammals (primates), then go on to birds, rodents, bats
  o then build a phylogenetic tree to see how close/ related the animal virus with the human virus is (if they overlap = highly possible reservoir species)
  o ex. ebola virus

 observed in bats trapped from areas near the disease outbreak
 three species of fruit bats shown to have very similar viruses which also overlap with the ones in humans

Question 14

host species and restriction factors

Answer 14

• some host species might not be affected from the viral infection due to the presence of restriction factors – which provide defence against getting ill from the viruses (not defence against infection)
• if the host coexists with virus long enough, viruses can evolve to be less pathogenic, and the host can evolve to be more resistant – which is a result of co-evolution (ex. myxoma virus & rabbits)

Question 15

extreme virus

Answer 15

Mimivirus
* Physically very big and contains a large linear dsDNA genome (1 Mbp)
* Contains 900 genes (a big jump from poxviruses with around 250 genes)
* Blurs distinction between cellular life and viruses – considered to be a 4th domain of life
* Has its own sputnik-virus – a virophage: viral phages that rely on the viral replication factory of a co-infecting giant virus for their own replication.

• Pandoraviruses are even larger with a genome size of 2.5 million base pairs
• Over 90% of its 2,500 genes have no identifiable homologs