BIOC0004 Introduction to Microbiology: Animal Virus PDF

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Summary

BIOC0004: Animal Virus What is virus? - Obligate non-living intracellular parasites that require a host to replicate  Absolute dependence on host cell  Cellular machinery to live and replicate  Can infect all types of life - Considered independent entity as it has its own genome  Occupy a partic...

Description

BIOC0004: Animal Virus What is virus? -

Obligate non-living intracellular parasites that require a host to replicate 

Absolute dependence on host cell  Cellular machinery to live and replicate

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Can infect all types of life

Considered independent entity as it has its own genome 

Occupy a particular environmental niche (a living host)

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Most ubiquitous and diverse group of organisms on the planet with a vast array not even yet been identified

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Disadvantage: invasion of living organisms in order to reproduce 

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Resulting in disease or death of the host

Selective advantage they afford to their host 

Can aid immune system’s proper maturation

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Can aid development of resistance to other similar viral infections – immunity

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Can affect and destroy bacteria/other viruses causing infections  a survival tactic of virus to last longer and get rid of competition

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Aid evolution by transferring genomic sequence among different species

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Can protect wildlife and help reduce global warming  Control algal bloom expansion, through a quasi-symbiotic relationship

Origin of viruses -

3 main hypotheses 

The Progressive Hypothesis (aka. escape hypothesis)  Mobile genetic elements that become autonomous and can move between cells – transposons  Driver of evolution

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The Regressive Hypothesis (aka. reduction hypothesis)  Derived from a more complex progenitor – a complex virus, or a type of mitochondrion

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The Virus-First Hypothesis (aka. the “RNA world”)  Viruses predate cells – exist as self-replicating units  Make the viruses the “first form of life” on Earth

Smallpox – history

Timeline in centuries – declared free of small pox at 1950 Common viral properties -

Small particles of genetic material, surrounded by a protein coat

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Build de novo in each generation

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Don’t have any cellular components

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Don’t have homeostasis

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Lack response to environmental stimuli

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Cannot be cultured

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Can reproduce only within living organisms  no archived records of them

Structure of virion

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Allow virus to travel from one host to another

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50% to 90% of mass is protein

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Capsid  put together by self-assembly  spontaneous assembly or help from host cell

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Envelope  phospholipid bilayer taken from host membrane  facilitate host entry and easy host exit

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Combination of nucleic acid and protein in virion  nucleocapsid

Genome structure

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A virus can have a DNA, or RNA genome and in some cases both (retroviruses) 

Only one type is present at any given time

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RNA viruses carry own polymerases (replicases) and usually replicate in the host-cell cytoplasm

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DNA viruses replicate in the host-cell nucleus

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Their great diversity in terms of morphology, genome, mode of infection, host range, tissue tropism etc. complicates their classification 

Nobel Laureate David Baltimore proposed a classification based on the nature of viral genomes and their modes of replication

The Baltimore scheme classification

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Grouped according to their mRNA synthesis mechanism 

All mRNA is designated as +ve and strands complementary to mRNA are designated as –ve

Virion morphology -

2x2 (=4) basic types of viral symmetry

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Enveloped (1) or naked (2)

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Viruses with similar morphologies may differ in all of their other fundamental characteristics

1. Helical – Rod a. “stacked-disc” with helical centre b. Symmetry of subunits are organised in helix c. Length of helical viruses depends on the length of nucleic acid (NA)

“Tobacco mosaic virus” TMV 2. Isometric – spherical a. Viral particles arrange with cubic symmetry b. Icosahedral symmetry is the most common c. Proteins assemble to symmetric cell to cover the virus

“Human Papillomavirus” HPV -

Morphology examples

Adenovirus

HPV

Herpes

Covid-19

HIV

Influenza

Tobacco mosaic Ebola

Hepatitis B

Rabies

Virion size -

From:

Circovirus (15nm in length, 1.75Kb, ssDNA) -

AAV (20nm in length, 4.7Kb, ssDNA)

To:

Pandoravirus (1µm in length, 2.7Mb, ddDNA)

Mimivirus (0.7µm in length, 1.2Mb, ddDNA)

Replication – life cycle overview

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Virion: complete, fully developed infection viral particle

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Host cells supporting virion replication: permissive 

Once virus attach, not available to attach to other cell  leads to penetration

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Attachment  virus attachment protein recognise and bind on cell surface

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Uncoating  loss of many, or all of the virus proteins

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While attaching to the host membrane or upon insertion

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In bacteria and archaea  only the nucleic acid enters host cell

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In plants and animals  the entire virion enters the host cell by endocytosis or fusion with membrane

Cell lysis  release some host cell membrane and use as the envelope

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Virus replication – one-step growth curve

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Phase: 1. Eclipse: genome replicated and proteins translated 2. Maturation: packaging of nucleic acids in capsids a. Number of infection agent increase dramatically 3. Latent period: eclipse + maturation 4. Release: cell lysis, number of virions released

Typical stages of a “typical” viral infection -

Affected individuals developing disease go through the following stages:

1. Infection  The organism invades and colonizes the host 2. Incubation period  The time between infection and onset of symptoms 3. Acute period  The disease is at its height 4. Decline period  Disease symptoms are subsiding 5. Convalescent period  Patient regains strength and returns to normal -

Example: seasonal flu

Types of viral infections

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Non-permissive  virus is not allowed cell entry

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Permissive  virus gains cell entry

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Types of permissive infection: 

Acute, or lysis – virus replicates, progeny is released and cell dies  Host quickly recovers or die in the process  Ex: influenza, Covid-19

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Persistent or chronic – Virus replicates, progeny is released, eventually infection is cleared, cell survives  Don’t affect all cells

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Latent– virus present in cell for life, may replicate  Eventually lead to cell lysis which has to do with host immune system  acute infection burst

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Transformation – virus causes cell immortalisation

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Abortive – virus enters the cell, but fails to replicate

Chain of infection

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Infectious diseases result from the interaction of agent, host and environment 

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Occurs when agent leaves reservoir and enter the host

The spread of an infection within a community: chain

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Several interconnected steps that describe how a pathogen moves about

Disease carriers and reservoirs

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Reservoirs: a population in which infectious agents remain viable (habitat) 

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Ex: bats  reservoir of a “zoonotic” diseases (disease that can be transmitted from animals to people)

Carriers: an individual that is pathogen-infection with no disease symptoms 

Asymptomatic, in the incubation period of the disease or convalescing

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Ex: Typhoid Mary

Co-evolution and co-adaptation of virus and host

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Viruses are not unchanging entities fixed for all time 

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Subject to evolutionary pressures and undergo constant evolutionary change

Overall: 

Host develops resistance to pathogen

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Pathogen develops countermeasure evasion mechanisms

Under evolutionary perspective: 

Well-adapted parasite must ensure survival of its resources (ex: its host)

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A pathogen that kills the host before it can infect another will become extinct

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Virus and host both aim to survive  exerting selective pressures on each other, co-adapting and co-

evolving -

Viral evolution – antigenic drif

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Antigenic drif:  Mutations to original viral strain that lead to a new strain  New strain can be closely related to progenitor  If so  host usually recognises the new strain and respond to it (“cross-protection”)  If not  the host can be re-infected by the new strain (about 25% success of flu vaccines)  Ex: flu (common cold), Influenza A and B

Viral infection distribution types

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Basic reproductive number – R0 

Number of cases arising from a single case

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How far and how fast a viral infection will spread

Endemic: constantly present at low incidence in a specific geographic area or population 

This population is considered a reservoir

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Not usually eradicated

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Ex: chicken pox (school yard disease)

Epidemic: occurs in a larger than expected number of people at the same time in a given location 

Zoonotic disease that goes through antigenic variation

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New pathogen  not immunity initially

Pandemic: a globalised epidemic 

Can with time become endemic

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Outbreaks = several cases in short time

Disease incidence and prevalence

The bathtub of epidemiology -

Incidence: number of new cases in a population in a given period of time

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Prevalence: number of existing and new cases in a population in a given time

Modes of transmission -

Direct: 

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Indirect: 

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Infected individual transmits a disease directly to a susceptible host without the assistance of an intermediary (ex: flu)

Occurs when transmission is facilitated by a living or non-living intermediary

Common vehicles: 

Food (ex: preparation)

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Fluids (ex: blood, water)

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Air (ex: airborne droplets)

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Living vectors (ex: animal bites)

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Zoonotic transmission (ex: animal contact, food chain)

Factors affecting relative disease incidence: 

Geographic location of carriers/reservoirs

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Climate (humidity, UV radiation)

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Circadian clock

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Virus and host migration patterns

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Socio-economic conditions (nutrition, sanitation, clean water)

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Genetic profiling (MHC I)  responsible to development of adaptive immunity (Major Histocompatibility Complex)

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Age at infection

Factors affecting disease severity: 

Cell type tropism

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Viral load

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Type of body entry

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Host immune system relationship  afer years, frequency of alleles that favour survival increases

Emerging and re-emerging infectious diseases

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Disease that suddenly become prevalent: emergent

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Diseases under control that become prevalent again: re-emerging

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Emergence factors: 

Human demographics and behaviour

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Technology and industry

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Economic development

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Land use

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Travel and trade

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Evolution – adaptation

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Breakdown in public health measures

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Climate changes

Representative viral disease of humans

Viral outbreaks and public health

Innate and adaptive immunity -

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Innate immunity  lead to redness and swelling of area 

Non-specific

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First line of defence

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Prevents disease spread

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Immediate response

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Cells: NK- macrophages, neutrophils, baseophils, eosinophils

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Antigen independent

Adaptive immunity (aka. Acquired/specific immunity)  only in vertebrates 

Antigen specific

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Second line of defence

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Fights disease and prevents re-emergence

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Long lasting

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Clonal expansion of T and B lymphocytes

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Antigen dependent

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Kick in later but highly effective and last longer

Passive immunity – antibody transfer -

Transfer of antibodies from one individual to another or manufactured

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Offers immediate but temporary protection

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2 types: 

Natural  maternal antibodies  In utero and afer birth

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Artificial  serum antibodies  Immunoglobulin treatment

Active immunity – vaccines -

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Functions: 

Prevent infection

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Control existing infection

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Prevent foetal infection through maternal immunisation

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Prevent/control cancer (ex: HPV and HBV)

Conventional: 

Live attenuated viral forms (ex: MMR)  tend to provide livelong immunity but risk of being active

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Inactivated viral extracts (ex: flu)

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Viral subunits (ex: HBV)

Newly developed: 

Recombinant viral components (ex: HPV)

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Viral vector-based (ex : Ebola, Covid-19)

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mRNA vacines (Covid-19)

Control of viral infections – Antiviral drugs -

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Infection management is mostly offered for: 

HIV

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Herpes family

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HBV, HCV

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Influenza A and B

Inhibition of:

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Host entry  using fusion inhibitors

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Retroviral genome integration  using integrase inhibitors

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Genome replication  nucleoside/nucleotide analogues

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Particle release  neuroamidase inhibitors

Challenges: 

Distinguish between virus and host

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Minimise building up of drug resistance

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Can have side effects

Herd immunity and infection transmission

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Definition: resistance of a group to infection due to immunity present in a large proportion of the group members

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Meaning: the whole population will be protected

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Reasoning: immunised people protect non-immunised people because the pathogen cannot be passed on and the cycle of infectivity is broken

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Percentage of immunity depends on how infectious the disease is

Measles and herd immunity

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“school-yard” viral infection  highly transmissive

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First vaccine licenced in 1964

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Intensive vaccination program initiated in 1968

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Herd immunity (through natural infection or vaccination) continuously protects the general population

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Re-emerging outbreaks are dealt with swifly

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Life-long immunity...