Viruses Flashcards
Important features of viruses?
Only able to function within the living cells of a host animal, plant or microorganism.
Consists of a nucleic acid molecule (DNA/RNA) surrounded by a protein coat, often with an outer lipid membrane.
Originally distinguished by their size.
Methods of studying viruses?
Pathology/transmission studies
Electron microscopy
Culture
Detection of virions and immune responses
X Ray crystallography
Nucleic acid detection, sequencing and analysis
Structure of a virus?
The virion is the infectious form of the virus outside of the host cell - fully developed.
Capsid is formed of one or more protein subunits and is tightly packed with viral DNA giving a large pressure. Once the tail tube is open it will unpack due to high pressure.
Virions have molecular receptors, of varying degrees of complexity, these enable recognition of and attachment to host cells.
Some bacterial viruses have mechanisms to inject their DNA into the host.
Some eukaryotic viruses are enveloped with a host-derived envelope.
Define bacteriophage?
Bacteriophage, also called phage or bacterial virus, any of a group of viruses that infect bacteria.
Differences between DNA and RNA viral genomes?
DNA:
- deoxyribose is less reactive due to C-H bonds
- stable in alkaline conditions
- smaller grooves make it more resistant to enzymatic attack
- mostly double stranded
- lower mutation rate
RNA:
- ribose more reactive due to C-OH bonds
- not stable in alkaline conditions
- larger grooves so more sensitive to enzymatic attack
- mostly single stranded
- higher mutation rate
Advantages of a segregated genome in RNA viruses?
Enables re-assortment and recombination of their genomes.
Important consequences for evolution and immune escape.
Influenza virus has 8 genomes.
Bacterial virus life cycle?
Virion gains entry Replication Transcription Translation Host-virus interactions Exit
Some phage can be latent in bacterial genomes. Insert to form a prophage (the genetic material to form a phage) in the host genome.
The lytic/lysogenic state is controlled by a genetic switch. Enables long term survival and introduces complex interactions of host and phage genome.
Pseudolysogeny normally occurs under nutrient deprivation when the host cannot support DNA replication.
Define pseudolysogeny?
Pseudolysogeny is a form of phage-host cell interaction in which the nucleic acid of the phage resides within its starved host in an unstable, inactive state.
Define lysogeny?
Characterised by integration of phage nucleic acid into the host’s (bacterial) genome.
Define lytic?
Results in destruction of the injected cell and its membrane.
Eukaryotic virus life cycle?
Virion enters the cell Transcription Replication Assembly Exit
How do viruses enter cells?
Receptor mediated endocytes.
Receptor mediated signalling causing fusion.
Both depend on displaying proteins which interact with cell receptors.
How does viral replication depend on genome structure?
Double stranded virus synthesises positive RNA strands from the negative strand.
Translated.
Synthesises negative RNA strands which are packaged into virions.
Positive RNA virus.
Translation
Creates replication proteins to create negative RNA which is then used to create positive RNA.
Retrovirus.
Uses reverse transcriptase to create DNA for integration into the genome.
Transcription creates +RNA.
Translated and packaged into the virions.
What happens in the Epstein-Barr virus?
Persistently infects almost all humans worldwide. Intrahost reservoir is B cells.
Normally a harmless passenger but can promote development of B cell lymphomas.
EBV can enable survival of B cell receptor deficient B cells.
EBV proteins also mimic cell signalling pathways.
Major EBV associated B cell lymphomas:
Burkitt lymphomas
Hodgkin lymphoma
Post transplant lymphoma
Retrovirus lifecycle?
Adsorption and entry into the cell Synthesis of reverse transcribed DNA Integration Transcription, splicing and nuclear export Translation and encapsidation Viral assembly and budding
What is an endogenous retrovirus (ERV)?
Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses.
They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.
Retroviruses invade the genome, can be inactivated by the loss of env gene, so become retro transposons spread within the genome
Virus evolution?
Might represent a 4th domain with a separate origin.
RNA viruses could be RNA world relics.
How do viruses get transmitted?
Direct transmission - physical contact Respiratory tract/airborne Gastrointestinal Sexually transmitted Vertically transmitted Arthropod borne (malaria in mosquitos)
What does the severity of the disease depend on?
Role of pathology in transmission Viral replication mechanism Host factors Tissue tropism - dangers differ based on tissue Acute or chronic phases of infection - latency Host immune responses Immune status and age of host Interaction with microbiome
Main features of parvo virus?
One of the smallest/simplest animal viruses.
Highly resistant virions can contaminate the environment for long periods.
60 protein subunits in the capsid, with single stranded DNA. Encodes two polypeptides which are processed to produce viral proteins by the host.
Replication in the nucleus using host replication machinery followed by assembly and release.
Not necessarily going to kill cells. Normally self-limiting infection of white blood cells, can cause a range of pathologies.
Main features of rabies virus? (Rhabdovirus)
Encodes 5 proteins.
Transmitted by biting.
Aggressive behaviour in the host is an essential component of disease.
Spreads through the host in neural tissue.
Replication cycle: virus particle is engulfed by a host cell.
Rabies virus glycoprotein fuses to the endosome membrane.
Viral RNA produced by the viral polymerase.
Forms viral mRNAs which are translated by the host into viral proteins.
Later there is generation of genomes
Virions are released from the host cell by budding
Transmission:
Rabies introduced by an animal bite. Enriched at neuromuscular junction and/or amplified/grows in muscle cells.
Virus enters neurone using NCAM receptor.
Rapid transport as whole virions through the neuron.
Once in the brain, the virus multiplies, changing behaviour, becoming more aggressive and killing the host.
Salivary glands are an important propagation site and exit route for the virions, completing the cycle.
Main features of influenza A?
ssRNA enveloped virus.
Nucleocapsid contains viral RNA, viral RNA polymerase and an endonuclease.
Envelope contains 2 viral proteins.
Genome replication and transcription and translation occurs in host cell nucleus.
Virus assembled and exported by budding.
A combination of viral and host factors (age, underlying health conditions) contribute to pathogenicity.
Main features of influenza A?
ssRNA enveloped virus.
Nucleocapsid contains viral RNA, viral RNA polymerase and an endonuclease.
Envelope contains 2 viral proteins.
Genome replication and transcription and translation occurs in host cell nucleus.
Virus assembled and exported by budding.
A combination of viral and host factors (age, underlying health conditions) contribute to pathogenicity.
Main features of HIV?
HIV is a retrovirus which attaches to a surface receptor. HIV has a latency period, before it may turn into AIDs (death of T cells).
Main features of HTLV?
Human T-cell leukaemia virus is a retrovirus, infects 20 million people worldwide.
The first retrovirus demonstrated to cause human cancer.
Initiates cell transformation by: generating chromosomal instability, and silencing p53 and spindle assembly checkpoints, amongst others.
Cell to cell transmission once inside the cell by fusing to others.
Main features of dengue virus?
Mosquito borne +ssRNA. 4 serotypes in tropical regions.
Capsid with 3 structural proteins – capsid, precursor and envelope. 7 non-structural proteins. Closely related to zika.
During a second dengue virus infection, the presence of pre-existing memory T/B cells alter the immune response – original antigenic sin, utilises immunological memory when a second slightly different version of the virus is encountered.
Can lead to severe life threatening haemorrhagic fever.
Occurs in a small proportion of individuals but infection is common so disease rates can be high.
Main features of zika virus?
Mosquito borne. Recent epidemics in Brazil associated with microcephaly in new-borns due to vertical transmission across the placenta, which targets foetal neural tissue.
This occurs when the mother was already immune before she became pregnant.
The epidemic rapidly spread then declined due to host population immunity.
