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
What is the vector for the West Nile Virus
Culex tarsalis
What type of hosts are humans for arboviruses
Deadend hosts- humans are not usually part of the life cycle.
Describe the presence of the West Nile Virus in New York
West Nile Virus belongs to Japanese encephalitis group of flaviviruses
WNV discovered in 1937, but mild disease
1956 outbreak in Eastern Europe with symptoms of increased severity
1999 in New York 61 cases, 7 deaths all > 50 years of age
Concurrently, birds in Bronx Zoo and wild crows became ill
West Nile Virus is an arbovirus that was not seen before 1999 on the American continent. It is not know how the virus crossed from Asia to the Americas. The replication cycle involves infection of mosquitoes and birds are the natural host. The virus has spread across the USA in less than a decade.
Discuss the potential origins of the West Nile Virus in New York
Subtractive differential analysis used to diagnose a human brain sample revealed WNV RNA
RT-PCR showed sequence identity with a virus circulating in Israel
Illegally imported bird?
Viraemic human?
Infected mosquito?
Describe Dengue
3 billion people live in at risk areas
50-100 million cases of DF each year; 300 000 cases of DHF
DHF case fatality 5%
Mosquito- borne febrile disease
RNA virus
It is also called break-bone fever because of the severe and painful backache, muscle and joint pain.
Describe the 4 main dengue serotypes
4 serotypes of DV cross reactivity but no cross protection- antibodies binding without providing protection is worse
Repeat infection of a second serotype, especially serotype 2 predisposes to a variant of disease called Dengue haemorrhagic fever, which causes haemorrhage or shock especially in children.
What does the spread of Dengue Haemorrhagic fever correlate with
upsurge in mosquito population
Describe the risk factors associated with Dengue Haemorrhagic fever
Virus strain Pre-existing anti-dengue antibody previous infection maternal antibodies in infants Age Higher risk in secondary infections Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission)
Why is antibody binding without protection dangerous
Fc binds to antigens, can be recognised by Fc receptors, virus taken into cells that it wouldn’t normally infect. It can enter macrophages, leading to cytokine storm, leads to leaky epithelial cells- haemorrhage.
Describe Chikingunya
associated with prolonged arthralgia
Similar symptoms to dengue fever
But more chronic than dengue
Describe the symptoms of the Zika Virus
Headache Pale skin, rash Fever Red eyes Diarrhoea Muscle pain, arthralgia
List the human viruses that have emerged from animals
Also Ebola, Hendra, Nipah which spill over but do not transmit efficiently
Why was Nigeria successful in reducing the spread of Ebola
Nigeria’s success story by contact tracing and containment
Describe Severe Acute Respiratory Syndrome SARS
Chain of human transmission began November 2002, Guandong province China.
Late February 2003 international spread.
July 2003 last chain of human transmission broken.
8422 cases in 29 countries, 916 total fatalities, 908 of them in China, Singapore, Canada, and Vietnam.
SARS coronavirus emerged in East Asia in 2003. The virus is normally found in bats. Farmed civet cats were an intermediate host in China for the evolution of a strain of the virus that could
attach to a receptor on human cells.
Describe the transmission and clinical epidemiology of SARS
Infected respiratory droplets; concentrated virus sources on lift buttons and in bathroom drains.
Amplified by use of nebulizers in hospitals.
Children experienced mild disease, patients over 60 years have 55% mortality.
Patients most infectious at 10 days post infection, when also symptomatic.
Destruction of lung tissue from overexuberant immune response.
Emergency response coordinated, international, rapid.
Direct or indirect contact of mucous membranes (eyes, nose or mouth).
Describe the characteristics of the SARS virus
Coronavirus; Large (30kb) positive sense RNA genome.
Envelope spike protein.
Receptor is human ACE-2 protein.
A virus almost identical isolated from masked palm civets and raccoon dogs in wet markets.
Chinese horseshoe bats harbour SARS-like coronaviruses that can use bat and human ACE2 as receptors.
S protein is highly plastic and can adapt to different receptors overcoming host range barriers.
What is meant by a super-spreading event
Few people are responsible for more transmissions.
Describe noroviruses
Noroviruses are small RNA viruses that cause diarrhoea and vomiting. There has been an increase in the incidence of norovirus disease in recent years. A new genotype of virus has emerged that appears to use a new receptor for host cell entry that is particularly widespread in humans.
Describe MERS coronavirus
Health tourism and business travel spreading the virus beyond Midde East
Closely related to HKU4 and HKU5 two bat coronaviruses
High seropositivity rate in camels
ARDS in older infected person but can be asymptomatic in infected contacts.
Zoonosis from camels
Target DPP4 receptors on lungs
What may be responsible for the next pandemic
MERS
Limited transmission
Diverse clinical signs
No vaccine, no antiviral
H7N9
Limited transmission
No vaccine but technology to make one is known
Antivirals but resistance tolerated.
Can some strains cause multiple pandemics
Yes- unexposed population grows to adulthood- HI1N1
Describe Man’s intervention as the cause of emerging viruses
Myxoma Virus released for rabbit control is Australia
Genetic manipulation creates a transmissible H5N1 influenza virus
Define zoonosis and host range barrier
New viruses that infect humans often cross over from animal reservoirs. The crossing of an animal pathogen into humans is called zoonosis. This does not happen very often because there is a host range barrier. This means that most viruses that are adapted to infect animal hosts are compromised in their ability to replicate and spread in humans due to the genetic differences between host factors the virus needs. Because humans have no pre-existing immunity to animal viruses they can cause devastating outbreaks or pandemics.
