Origin, evolution and emergence Flashcards

1
Q

Where do viruses come from?

A
Controversial topic
3 Theories proposed: 
“Virus first” theory
Reduction theory
Escape theory

Unlike animals, no fossils to study therefore evidence scanty

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2
Q

Virus first theory:

A
  • Remnants of pre-cellular forms
  • Primordial “RNA world”
  • Existed as self-replicating units which became more organized and more complex over time – developed enzymes for membrane synthesis
  • Present RNA viruses could be relics of RNA world
  • Retroviruses: relics of RNA/DNA transition
  • Theory rejected because viruses are obligate intracellular parasites

Notes:
Viruses are obligate intracellular parasites.
Theory of evolution
Primordial=existing from the beginning of time.

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3
Q

Reduction theory:

A
  • Descendants of unicellular organisms that over time, adapted a parasitic replication strategy
  • Symbiotic relationship between organisms but over time one organism became dependent on the other, eventually losing it’s essential genes.
  • Poxviruses – large complex genome, depends less on host cell for replication
  • Theory rejected because no known intermediate form between cells and viruses. Also, if viruses derived from cells, would retain cellular characteristics.
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4
Q

Notes on the reduction theory:

A

*May be descendants of previously free-living organisms that adapted a parasitic replication strategy
*Autologous organisms developed a symbiotic
relationship
*Overtime the relationship became parasitic with one organism depending on the other and lost essential genes
*Poxviruses illustrate this hypothesis
large genome size with greater complex
depend less on host cell for replication

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5
Q

Escape theory:

A
  • Viruses came from fragments of cellular genetic material capable of moving within a genome.
  • Gained ability to exit one cell and enter another
  • Escaped from the control of the cell and became parasitic
  • Theory favoured because present-day viruses can integrate cellular genes into their own genomes.
  • Drawbacks: Doesn’t specify how nucleic acid acquired a capsid. Also viral proteins have no cellular homologues
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6
Q

Notes on the escape theory:

A
  • Viruses originated through progressive process
  • Views viruses as elements of cell genome
  • Viruses originated from fragments of mobile genetic material capable of moving within a genome
  • Gained ability to exit one cell and enter another
  • Escaped from the control of the cell and became parasitic – plasmids and mobile elements are considered precursors
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7
Q

Virus evolution

A

Viruses have a greater genetic diversity than any
other group of organisms
Diversity produced by natural selection acting on genomes that are continuously changing as a result of:
mutation
recombination
reassortment

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8
Q

Viral replication:

A

Viral replication →millions of progeny virions
Errors are inevitable→ mutations
lethal
disadvantageous
neutral
selective advantage
Def: localized inheritable alteration of the nucleotide sequence of a nucleic acid

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9
Q

Mechanisms - mutagenesis

Types

A

Spontaneous
Template miscopying by the viral RNA/DNA polymerases –
chance errors during replication
Activity of cellular enzymes i.e. deaminases

Induced
chemical damage to the viral nucleic acid eg. nitrosoguanidine
physical agents – UV light, irradiation
use of base analogues – mutagenic when viruses are grown in their presence
site-specific mutagenesis – genetic engineering

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10
Q

Notes on RNA viruses:

A

RNA viruses have higher mutation rates than DNA viruses
RNA polymerases – one mistake per 103 to 105 nucleotides incorporated
Error-rate of RNA replication&raquo_space;> DNA; lack of proofreading
mechanism
Rate of base substitution is ~106 times higher than Euk DNA
Most substitutions are deleterious
Non-lethal mutations in the genome accumulate very rapidly
Mutations continue to accumulate in the viral genome during passage in cultured cells, just as they do in natural replication in the host

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11
Q

Notes on DNA viruses:

A

DNA viruses:
Replicate in the nucleus ~ similar to error-rate of DNA in eukaryotic cells
Proofreading exonuclease error correction
Error-rate: one mistake per 107 to 109 nucleotides incorporated

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12
Q

Emerging & Re - emerging viruses:

A

Interface between humans, animals, & environments  source of diseases impacting public health
Zoonoses = infections transmitted from wild or domestic animals to man
Emerging Viruses = Viral infections that have newly appeared or that have appeared previously, but are expanding in incidence & geographic distribution or threaten to increase in near future”John R Su, Clin Lab Med 24 (2004) 773-795
Emerging = Newly discovered
Re-emerging or Resurgent = Re-appearing

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13
Q

Notes on emerging & Re - emerging viruses:

A

Most human viral infections maintained in nature within animals
Many viruses efficiently transmit between different species

Majority of emerging viral infections are zoonotic - due to microbial traffic - transfer of existing agents to new host populations
Introduction of viruses into humans often due to human activities
Viral zoonoses occur in variety of ecological settings
Very limited ecological & geographical foci
Viruses cause little or no overt disease in animal host
Some zoonotic viruses very limited host ranges
Others may infect a wide range of vertebrates
Human infection - Asymptomatic or mild to severe or life threatening depending on specific virus & immune response
Potential for epidemic spread or pandemics

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14
Q

Examples of emerging & Re - emerging viruses:

A

Animal RNA viruses  common source of emerging viruses
RNA viruses lack proofreading  high error rate during replication  high mutation rate
Most RNA viruses  zoonoses  transmitted initially to humans from mammals or avian hosts e.g. influenza, Nipah, SARS, MERS viruses
Some viruses commonly transmitted exclusively between humans - HIV & HCV - likely animal origins

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15
Q

The infection of emerging & Re - emerging viruses is acquired by:

A
Direct contact with animal 
Ingestion of meat or animal products 
Contact with animal urine or faeces 
Aerosol inhalation 
Arthropod vector  
Inoculation of saliva in a bite wound
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16
Q

Global emerging infections since 1973:

A
1973		Rotavirus			Enteritis/Diarrhea
1976		Cryptosporidium		Enteritis/Diarrhea
1977		Ebola virus			VHF
1977		Legionella 			Legionnaire’s Dx
1977		Hantaan virus		VHF HRS
1977		Campylobacter		Enteritis/Diarrhea
1980		HTLV-1			Lymphoma
1981		Toxin prod. S.aureus	Toxic Shock Synd.
1982		E.coli 0157:H7		HUS
1982		HTLV-II			Leukemia
1982		Borrelia burgdorferi		Lyme disease
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17
Q

Global Emerging Infections since 1983:

A
1983		HIV				AIDS
1983		Helicobacter pylori		Peptic Ulcer Dx
1988		Hepatitis E			Hepatitis
1989		Hepatitis C 			Hepatitis
1990		Guanarito virus		VHF 
1991		Encephalitozoon 		Disseminated Dx
1992		Vibrio cholerae O139	Cholera
1992		Bartonella henselae		Cat Scratch Dx
1993		Sin Nombre Virus		HPS
1994		Sabia virus			VHF
1994		Hendra virus			Respiratory Dx
1995		Hepatitis G 			Hepatitis
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18
Q

Global Emerging Infections since 1993:

A

1995 H Herpesvirus-8 Kaposi Sarcoma
1996 vCJD prion Variant CJD
1997 Avian influenza (H5N1) “Bird” Influenza
1999 Nipah Virus Encephalitis
1999 West Nile Virus Encephalitis
2001 Bacillus anthracis Anthrax
2003 SARS-CoV SARS
2009 Influenza H1N1 “Swine” Flu
2013 MERS-CoV MERS
2015 Zika virus Congenital defects
2019 SARS- CoV2 COVID-19

19
Q

Impact of emerging viruses:

A

Over the past century, humanity has witnessed the emergence of numerous zoonotic infections that have resulted in varying degrees of human fatalities. Influenza viruses originating from birds account for an important portion of these deaths and recently many new zoonotic viruses originating in bats, such as Hendra virus, Nipah virus, and severe acute respiratory syndrome coronavirus (SARS-CoV), have caused outbreaks with high mortality rates.
New novel coronavirus= acute respiratory illness

20
Q

Viral factors:

A

Recombination: 2 viruses
co-infect cell e.g. SARS
Re-assortment: segmented viral genomes e.g. influenza
Point Mutation: mostly RNA viruses, lack of proof-reading

Re-assortment leads to genetic diversity

Genetic diversity gives rise to:
Change in host range -
    cross species barrier
Altered tropism
Escape immune surveillance 
   & clearance
Drug resistance
21
Q

Human factors

A
Population growth
Urbanization   overcrowding
Poverty, crowding, social disorder, mobility & political instability
Human population movements      
Globalization of travel & trade 
Warfare & population displacements
Agricultural practices & deforestation 
Live animal markets 
Intensified livestock production
Wild animal hunting & trade e.g. HIV
22
Q

Ecological/Environmental Factors:

A

Disturbance of natural ecosystems & their various internal biotic controls deforestation, biodiversity loss
Intensified exploitation of natural environments & food production.
Global climate change

23
Q

Factors influencing emergence:

A

Several factors, including the recent growth and geographic expansion of human populations and the intensification of agriculture combined with habitat disruption caused by climate change and deforestation, has meant that now, more than ever, there is a greater risk of emerging infectious diseases (EIDs) being transmitted to humans from wild and domesticated animals. Moreover, increased global travel means there is a greater likelihood that EIDs will rapidly spread. Over the past three decades the incidence of EIDs has risen in humans, with around 70 percent being zoonotic in nature, and the majority being caused by viruses.

24
Q

Microbes as Co-Habitants:

A

Microbes’ interest  survival & reproduction.
No evil intent morally neutral!
Humans, domestic animals & wildlife
linked by epidemiology of infectious diseases (IDs).
IDs  continue to emerge, re-emerge & spread.
Human-induced environmental changes, inter-species contacts, altered social conditions, demography & medical technology affect microbes’ opportunities.
New research, technology & collaborative networks  early detection & control

25
Q

Laboratory role in identification of “Novel Viruses”:

A

“All Catch” Methods
Isolation
Electron Microscopy

‘Best Guess” Methods
Molecular assays : e.g. PCR using random primers

Immunological assays: e.g. polyclonal or “X”reactive antibodies

“Finding a match” -Using cDNA library for immunoscreening e.g. HCV

26
Q

Notes on HIV:

A

The currently defined groups of HIV-1 (M, N, O, P) and the HIV-2 groups A through G each are likely derived from a separate transfer to humans from a nonhuman primate reservoir. HIV-1 viruses likely came from chimpanzees and/or gorillas, and HIV-2 from sooty mangabeys. The chimpanzee subspecies Pan troglodytes troglodytes has been established to be the natural reservoir of the HIV-1 M and N groups. The HIV-1 O group is most closely related to viruses found in Cameroonian gorillas. Origins of HIV-1 and HIV-2 - cross-species transmissions of SIVcpz and SIVsm respectively - probably due to direct human contact with infected primate blood on multiple different occasions in Central Africa. Sequence evolution analyses place the introduction of SIVcpz into humans that gave rise to HIV-1 group M at about 1930, although some estimates push the date back to about 1908. Social, economic, and behavioral changes that occurred in the mid 20th century provided circumstances that allowed HIV to expand, become well-established in humans, and reach epidemicproportions.

27
Q

Rabies:

A

2021 – 19 cases in SA
2020 – 7 cases
2019 – 10 cases
2018 - 13 cases
2017 - 7 cases
2016 - 2 cases
Increasing rabies cases relates to outbreak of dog rabies in KwaZulu-Natal and Eastern Cape
Public is urged to ensure dogs & cats are vaccinated against rabies
Possible exposure  Urgent medical attention
2019 – 2 cases in EC, 1 in Limpopo, 1 in KZN

28
Q

SARS Coronavirus:

A

2002-2003
Guangdong Province, China
“ outbreak of atypical pneumonia”
Approx. 300 cases in China
Spread to other countries –
Over 8000 probable cases from 32 countries
Non-segmented (+) ssRNA virus - coronavirus family
Origin: Zoonotic transmission from civet cats.
Natural reservoir: Chinese horseshoe bats.
Transmission – respiratory droplets, direct contact, fomites.
No vaccine available

29
Q

Notes on SARS Coronavirus:

A

SARS-CoV - Nov 2002 – emerged in China, spread to other countries. By the end of the worldwide outbreak in July 2003 - 8096 cases reported with 774 deaths - case-fatality rate of 9.6%. 21% health care workers infected. Minimal homology to existing classes. Origin - Zoonotic transmission from civet cats. Natural reservoir – Chinese horseshoe bats. Transmission – respiratory droplets, direct contact, fomites.

30
Q

Notes on Coronaviruses:

A

MERS - 2012 - male patient in Saudi Arabia with pneumonia and acute kidney injury - subsequent cases and clusters of infections reported. Novel coronavirus discovered - Middle East respiratory syndrome coronavirus. At the end of September 2018, a total of 2260 laboratory-confirmed
cases of MERS, including 803 associated deaths (case-fatality rate: 35.5%) were reported globally; the majority of these cases were reported from Saudi Arabia (1882 cases, including 729 related deaths with a case-fatality rate of 38.7%). Animal origin – Reservoir - closely related to bat coronaviruses, Intermediate host – camels. Human-to-human transmission occurs – droplet, contact. Incubation period – 5-14 days. Pneumonia, acute respiratory distress syndrome, acute kidney injury. Lower respiratory tract specimen preferable than upper respiratory tract for PCR.

31
Q

MERS stands for:

A

Middle East Respiratory Syndrome

32
Q

PCR stands for

A

Polymerase Chain Reaction

33
Q

Notes on MERS Coronavirus:

A

No vaccine
General hygiene measures  hand washing
IPC  Environmental IPC
Avoid
Farms, markets, barns, places where camels & other animals
present
Contact with sick animals
Raw or undercooked animal products, including milk & meat
Cooking/pasteurization safe for consumption - handle with care to avoid cross contamination with uncooked foods.
Chronic Diseases - diabetes, renal failure, chronic lung disease & decreased immunity - increased risk of severe disease

34
Q

IPC stands for

A

Infection prevention and control

35
Q

SARS CoV2:

A

Emerged in Wuhan, China and caused the COVID-19 pandemic
Related to SARS and MERS,
Currently estimated 5,8m deaths globally
Severe respiratory illness, especially in high risk groups
Diagnosed by PCR or antigen tests
Prevention: general measures e.g. handwashing, masks, distancing and specific measures e.g. vaccines
Antivirals developed e.g. Remdesivir; Monoclonal antibodies
Variants have been detected
Has caused global disruption and severe strain on healthcare systems

First three cases with similar LRTI symptoms identified in Wuhan, December 2019
LRTI - Lower respiratory tract infection

36
Q

Zika Virus:

A

First identified - 1950s - Uganda - infected monkeys
Discovered in Aede Africanus mosquitos in Zika Forest
Isolated in humans in Nigeria (1968), other African countries & Asia
Emergence in Americas in May 2015
Flavivirus: Yellow Fever, Dengue, West Nile Virus.
Reservoir: not known, Transmission: mosquito-human-mosquito
Human-human transmission rare- documented case of sexual transmission; Mother to child transmission- microcephaly
No specific antivirals or vaccine, Vector control, Counselling of women of child bearing age & pregnant females to avoid endemic areas

37
Q

Prevention:

A

Health of people connected to health of animals & environment
Surveillance - animals, humans, vectors
monitoring animal populations at sentinel locations  alert to risk
Vaccine - animals, humans
Vector control
Education & Training - public, health care workers, high risk groups or communities
Reduce occupational exposure risks - hunters, food handlers, & livestock workers
decrease in hotspots of emerging IDs  routine sanitation & biosafety precautions
decrease in Nosocomial spread - stringent adherence to IPC practices
Outbreak Response, Improve infrastructure & Applied Research

38
Q

Prediction of the next pandemic Zoonosis:

A
  • Discovery of a virus can predate its emergence as recognized public health threat
  • Discovery of Zika virus in a monkey in Uganda occurred in 1954, however caused widespread epidemic in 2015-2016 in Americas when it was discovered to cause congenital abnormalities  declared a public health emergency of international concern
  • No pandemic has been predicted before infecting human beings
  • Is it feasible to predict which animal viruses have potential to cause disease in humans?
  • Not yet possible using sequence data alone to predict probability of an animal virus transitioning to humans
39
Q

Notes on the prediction of the next pandemic Zoonosis:

A

Sequencing and cataloging the viruses of animals in selected areas can provide valuable insight to transmission dynamics and phylogenetics but cannot yet be used to predict. Ultimately, the best indication that a pathogen has the ability to jump to humans is finding it in humans.

40
Q

Emergence of Pandemic Zoonotic Disease:

A

Stage 1: Pre - Emergence
Human encroachment into the wildlife habitat. Change in land use

Stage 2: Localised Emergence
Expansion of wildlife - human interface
Nipah Virus
Ebola Virus

Stage 3: Pandemic Emergence
International trade and travel
*HIV/AIDS
SARS

41
Q

How do we predict the next Pandemic Zoonosis?

A

Geospatial models - identify regions most likely to produce next emerging zoonoses  “GLOBAL HOTSPOTS” of emerging infectious disease
Phylodynamics - understanding patterns of viral evolution during epidemics
Surveillance Programmes: Emerging Pandemic Threats Programme - PREDICT component -sampled >6000 animals in Sierra Leone – discovery of a new ebolavirus - Bombali virus (BOMV) detected in free-tailed bats
Understanding viral, human and environmental factors of emergence

42
Q

Notes on how to predict the next Pandemic Zoonosis:

A

Human contact with an animal virus does not ensure infection. Among the biological barriers for the virus are finding a route of entry, evading general immune defences, invading host cells, replicating sufficient numbers before specific immune responses are mounted, and finding a route to the next host. In general, vertebrate specificity greatly limits the ability of viruses adapted to one species to invade similar cells in another, distant species. The species richness of the tropics suggests that human populations there are exposed to greater risk and that they are fertile grounds for virus mutation

43
Q

Closing points:

A

Most recent pandemics - HIV, SARS & pandemic influenza - caused by zoonotic viruses - originated in wildlife
Infections usually driven to emerge by ecological, behavioural, or socioeconomic changes
Technological advances in mathematical modelling, diagnostics, communication & informatics  targeted global surveillance of emerging & previously unknown infections in humans & other species