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Lecture notes

60+ PDF Molecular Virology Study Notes
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The content covers 15 lectures and includes 168 PDF pages - the actual notes are not this long, the visual aids take up some space. Topics covered: - Virus definition - Viral structure, genes and proteins - Viral entry - Viral replication - Picornaviruses, Herpesviruses, Retroviruses - Vi...

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  • February 13, 2024
  • 168
  • 2023/2024
  • Lecture notes
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1- Virus genomes and proteins
Learning objectives:
• Broad understanding of virus genome diversity
• Appreciation of viral structure affects its replication
• Understanding of virally encoded proteins and their functions

Definition
A virus consists of a nucleic acid surrounded by a protein coat. They can be quite large (viewed
under light microscope) and very small around 0.02 micrometres. Viruses are not cells but are
nucleic acids surrounded by a protein coat and therefore acellular

Virus genome types
Viruses genomes can be encoded as either
• RNA
• DNA
And have a variation of being either single or double stranded:
• ssRNA genome
• dsRNA genome
• ssDNA genome
• dsDNA genome
They can be either:
• Linear
• Circular




RNA viruses
These viruses are distinguished via the following features:
• ssRNA or dsRNA
• ssRNA can be either positive sense or negative sense
• dsRNA is nonenveloped
• Negative sense is only enveloped
• Positive sense can be enveloped or non-enveloped




Molecular Virology-MICR2121 Page 1

,RNA viruses have the following characteristics:
• Small genomes (3-32 KB) because carry own RNA polymerase although this polymerase
doesn’t proofread so is error prone. As a result can respond rapidly to evolutionary pressures
and is a quasi- species: species that is slightly different to one another
• Mostly ssRNA and one family of dsRNA
• ssRNA can be:
○ +ssRNA- positive sense
○ -ssRNA - negative sense

Positive and negative sense
The central dogma states DNA makes mRNA which makes protein. mRNA and DNA can be
interchanged while protein can never change back into mRNA or DNA. RNA viruses completely miss
out the stage of transcription and only undergo translation. Negative sense or antisense RNA is only
complementary to the mRNA needed in translation and must first be converted to positive sense
before.




Positive sense
Genomes can be translated directly into virus proteins therefore their genomes are mRNA (share
some structural features of mRNA).
Must therefore undergo translation and therefore have a 5' cap (7-methylguanosine) and/or 3' end
(poly-adenosine)

Molecular Virology-MICR2121 Page 2

,(poly-adenosine)
Examples include: Picornaviruses, Togaviruses, Flaviviruses, Coronaviruses and Retroviruses




The positive sense virus mRNA directly inserts itself into translation and misses out transcription

Structure of 5' cap
• Required for initiation of translation
• lasts a lot longer than other RNA as its 5' cap provides resistance to various exonucleases
produced by the host cell (e.g. Xrn I)

IRES: Internal Ribosome Entry Sites
IRES is an alternative way to carry out translations. Some RNA viruses do not have the 5' cap. They're
still translated as their genome can fold up to form RNA secondary structure. Hydrogen bonds form
specific RNA stems which act as a cap and translation can still occur. Same can happen at 3'
polyadenosine tail.

Types of +ssRNA virus

1) Flaviviruses
• Dengue fever virus, yellow fever virus, west nile virus, tick borne encephalitis
• Genome size approx. 11KB
• enveloped
• All contain a 5' cap and 3' tail and looks like mRNA.




• Translation occurs and the long mRNA is then cleaved into individual viral proteins
• Hepatitis C virus is an example of +ssRNA that uses IRES

2) Picornaviruses
• Includes poliovirus, Rhinovirus, Hepatitis A virus
• Genome size approx. 7.5KB
• Has IRES
• Non-enveloped
• Single ORF encodes polyproteins of 2,200 A.A which is then cleaved

3) Alphaviruses

Molecular Virology-MICR2121 Page 3

, 3)Alphaviruses
•Eastern equine encephalitis virus, Chikungunya virus, sindbis virus
•Genome approx. 12Kb
•Has 5' cap and 3' tail
•Contains two open reading frames that encode two polyproteins (2500 and 1250 A.A long)
which is then cleaved into individual polypeptides
• ORF 1- produces non-structural protein
• ORF-2 produces structural protein




4)Coronaviruses
•SARS (severe acute respiratory syndrome), MERS (middle east respiratory syndrome)
•Genome approx. 33KB- one of biggest +ssRNA
•Can be very large due to unique RNA polymerase has proofreading capability so can translate
and correct, so genome can be big
• Method of replication a bit more complicated than smaller genomes
• Has multiple ORF's
• Instead of the mRNA being directly translated, the +ssRNA is converted into a full length -
ssRNA and is then transcribed into individual mRNA. Therefore it's not translated into a large
polyprotein then cleaved but transcribed into separate RNA. This occurs in the cell. The switch
from positive to negative sense means its transcribed from the 3' polyA tail first.




5)Retroviruses
•Moloney Murine Leukaemia Virus (Mo-MLV), Human T Lymphocyte virus (HLTV), HIV
•Genome structure approx. 9-11 KB
•Contains 5' cap and 3' polyA tail and LTR (long terminal repeats- identical sequences of DNA
that repeat hundred/thousands of times).
• Replicates via duplex DNA copy- reverse transcription





Molecular Virology-MICR2121 Page 4

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