Microbiology 7- Evolution and emergence of new viruses Flashcards
Describe the evolution of viruses during human circulation
Within host evolution of HIV. The quasispecies that exists within a single infected person contains every single mutation at every single position in the genome.
The virus may encounter a bottleneck at transmission or during replication under limiting conditions
Drug or immune response that targets one site will lead to selection of beneficial mutations.
What is meant by a quasispecies
progeny different to the others, each copy of the genome may contain errors, due to errors in reverse transcriptase.
Describe a bottleneck
Modest transmission, only few will be able to spread, but then diversity will accumulate,
Describe the relative fitness of resistant strains
nd if such a mutation leads to a coding change in a target for a drug of antibody then that mutant virus will be fitter than its sister progeny under conditions where the drug is used.
Drug resistance thus occurs readily in the treated patient. The resistance mutation sometimes confers a fitness cost to the virus and this means the resistant virus is unlikely to spread beyond the treated patient. If there is no fitness cost then the drug resistant virus can predominate and render use of the drug redundant.
What features of viruses contributes to antiviral resistance
High mutation rate and large progeny numbers and short replication time make viral evolution in response to selective pressure very fast.
Relative fitness of drug resistant virus vs wild type virus in vivo can influence whether drug resistant viruses proliferate.
RNA viruses are particularly prone to generate many errors during their replication because their RNA dependent RNA polymerases lack proof reading activity.
Explain the rationale for multi-drug therapy
Multiple HIV targets encoded by different regions of the genome, hence if resistant to one target it will not be resistant to another (error rate is 1 in 10^4 in a 10kb genome). Hence we need to have drugs against different targets, to reduce selection for resistant strains.
As well as antiviral drugs, what else can be a selection pressure for viral evolution
Antibodies.
Describe antigenic drift
During viral replication mutations can occur in the HA or NA, leading to changes in antigenic nature of these glycoproteins. This is termed antigenic drift. The resulting new strains are only partially attacked by our immune system, resulting in milder disease in adults who have previously acquired antibodies. Major histocompatibility changes usually result in altered codon reading frames and a nonviable virus.
Describe antigenic shift
With antigenic shift there is a complete change in NA, HA or both. This can only occur with influenza A because the mechanism involves the trading of RNA segments between animal and human strains. When 2 influenza types co-infect the same cell, undergo replication and capsid packaging, RNA segments can be mispackaged into another virus. The virus wields a new HA or GA glycoprotein that has never been exposed to the human immune system anywhere on the planet. So the entire human population would be susceptible, leading to devastating pandemics.
The new virus may displace any circulating viruses.
Why do we need to update viruses every year
Vaccine updated every year to best represent the circulating strains- to account for antigenic shift and drift.
How do new viruses emerge
Zoonosis Genetic variation Increased exposure- travel or world population Increased exposure- spread of vector New discoveries
Why are we all susceptible to zoonosis
No previous exposure
Describe new viruses that have only been recently discovered or detected- but may have been there before
‘Non A non B’ hepatitis caused by hepatitis C virus
Human papillomaviruses 16 and 18 as cause of cervical cancer
HHV8 as cause of Kaposi’s Sarcoma noticed during the AIDS pandemic
Merkel cell polyoma virus identified in tumours as non human sequence
Describe the global influences on emerging infections
Environmental modification; demographics World population Climate change Travel Farming practises; monocultures Immunosuppressed humans Medical progress Spread of arboviruses due to climate change.
Describe arboviruses
Yellow fever; Dengue; West Nile; Zika; chikingunya;
Flaviviruses and alphaviruses; positive sense RNA genomes
Mosquito host
Global warming, decrease in mosquito control, imports, stagnant water in large cities, dams
