viruses and pandemics

lecture 7 to lecture 12

infectious (communicable) disease 

Are transmitted from one person to another by: 

• Direct physical contact 

• Handling the same objecy 

• Via a diesease carrier (by a vector eg mozzies) 

• Aerosols (eg droplets in air) 

Non-infectous (non-communiable) disease 

Also know as chronic disease (meaning they tend to be of longer duration) 

Caused by variety of factors: 

• Genetic 

• Physiological 

• Environmental 

• Behaviour (lifestyle, diet etc) 

• Eg cardiovascular disease

How do we measure disease 

Epidemiology – the study of disease in a population 

• Eg dr john snow and the broad street cholera outbreak 

• Track people who got cholera lived on map to see if there were any patterns 

• From this, piece together that seemed to be clustered around specific water fountains 

• Collected enough data to identify three specific pumps, told people not to drink water from these pumps, found outbreak died down 

measures of disease

Direct measures 

• Viral titres 

• Bacteria load 

Indirect measures 

• Antibody against pathogen 

• CD4 cell levels (as in HIV) 

prevalence

How many have a disease 

• Point prevalence (at any given point in time, how many people have this disease) 

• On 2nd july 2023, point prevalence for covid was 126 per 100,000 

Period prevalence (over a period of time, how many people have this disease, gives idea of scale) 

• On 2nd july 2023, the period prevalence of covid from the start of the pandemic is 46,543 per 100,000 

Lifetime prevalence 

incidence

• How many NEW cases in a period of time 

• Incidence is a rate 

• Eg for the week ending 2nd july 2023, there were 6,578 new cases. This rate of new cases per week is the incidence 

What is a virus 

Viruses are incredibly diverse (in morphology, how they infect organisms, which organisms they infect etc) 

• Virues infect all forms of life (bacteria, animals, plants, archaea, fungi, algae, protists) 

• They shaped human evolution (Large scale incprporation of viral genomes in the human genome)

Responses to epodemics/pandemic 

• Enable the development of molecular biology tools (Eg cloning)

Majority of viruses that infect humans do not affect out health but some do:

• Covid-19 and other global pandemics 

• Huge burden of disease 

• Large effect on economy etc due to illness of workers Eg seasonal flu and cold 

• Some viral infections are never fully cured Eg HIV-2 

Smallpox 

Caused huge burden of disease 

some evidence of smallpox in 3rd and 4th century (been around for ages) 

High fatality rate – 300 million deaths in 20th century 

• had a large impact on vaccine development 

Variolation-vaccination 

• Give healthy person defence by giving them a little bit of smallpox (scratch of pustule into healthy person as vaccine 

• Someone noticed some people working around cows got cowpox, similar in presentation to smallpox 

• People who got cowpox didn’t tend to get smallpox 

• He took material from cowpox pustule and infected small child with cowpox, later when he tried to infect them with smallpox, it didn’t take 

• Despite this, they still had no real understanding of what caused it – variola virus 

Tobacco mosaic disease (TMD) experiment 

• Decided to filter to see if they could isolate virus 

• Development if filters with 1 µm pores (Excludes most bacteria) 

• Filtrate from TMD-infected plant could still cause TMD 

• Didn't know what a virus was, very small bacterium? Chemical- biological toxin? 

• Must use electron microscope to see, tiny 

• Filter was able to exclude plant cells and bacteria, end up with liquid with disease causing particle in it.  

Viruses as a pathogen 

Pathogen: 

• Organisms capable of causing disease in a host 

Virus: 

• Submicroscopic, obligate parasite (must have host) 

• Acellular, composed of a nucleic acid (DNA or RNA) core inside a protein coat 

• Because they are not cellular, they are not included in “tree of life: 

• Dependent on infecting a host cell to use the host cellular machinery in order to replicate and survive = obligate paracite 

• Viron: single virus particle 

Classifying viruses 

• Done by international committee on taxonomy of viruses (ICTV) 

• Classified into realms 

• Development of this classification system in ongoing 

As of 2026, now 10 realms 

• Efunaviria 

• Pleomoviria 

• Singelaviria 

• Volveviria 

Classifying animal viruses 

• Subset of viruses that infect animals, some of which also causes disease in humans, can be further classified based on viral characteristics 

1. whether or not the virus has an envelope 

• Enveloped or not enveloped 

2. The type of genome 

• This classification is sometimes referred to as the Baltimore classification system 

• Important for understanding how different viruses replicate 

Cellular genomes: 

• All cellular life forms have genomes consisting of double-stranded DNA 

• Inherited from parents and transmitted to offspring 

• Encodes info essential for cells activity (eg metabolism) 

• The flow of genetic info: DNA--> undergoes transcription---> RNA ---> undergoes translation---> protein 

viruses characteristic

• acellular

• obligate intracellular parasites

• DNA or RNA (never both)

• capsid

• envelope (sometimes)

diversity of viruses

• Can have DNA or RNA (never both) 

• Vary in size (3 vs ~2,000 genes) 

• Variety of forms (single-stranded(ss), double –stranded(ds), linear, ircular, segmented) 

• Means there is a whole lot of ways viruses can infect and impact host cells 

capsid

• Protein coat then encapsulates the viral genome 

• Made up of protein subunits called capsomeres 

• Number/arrangement of capsomeres can be used to identify viruses 

• Role in attachment ot host cells in some viruses 

• Influcences shape 

shapes of viruses

Polyhedral: 

1. Many sided, most commonly icosahedral (20 triangular faces) eg poliovirus 

Helical: 

1. Repeating protomer arranged in a spiral around the nucleic acid eg TMV 

Complex 

1. Combination of helical and polyhedral shapes eg bacteriophages 

Envelope 

• Only some viruses have an envelope 

• A membrane acquired from host during virion assembly 

• “bud” - acquired as they move throughthe host cell membranes (eg plasma membranes) 

Virus derived envelope proteins – spike proteins (glycoproteins) 

Some enveloped viruses also have spike proteins 

• Glycoproteins that extend from the capsid 

• Involved in attachment to specific receptor sites on the host cells (eg covid) 

• Can help ensure specificity (infect certain cells) 

• Certain pes cause haemagglutination or clumping of red blood cells (eg haemagglutinin spikes (H), influenza virus) 

examples of envelope affecting shape

• Herpesvirus 

• Has a polyhedral capsid but the overall shape is spherical because of the envelope 

• Poxviruses (eg monkeypox) 

• Classified as complex viruses due ti the complexicity of the envelope 

• Shape can help identify which form of virus (mature vs immature, stage of infection 

Pros: 

• Help evade immune system, hidden from host immune systen (host cannot identify pathogen if encapsulated) 

• Fusion with host cell/plasma membrane --> infection 

• Release new virions without destroying the host 

Cons 

• More susceptible to environmental damage (temp, pH) and chemical disinfectants 

Viral specificity  

host range and cellualr/tissuse tropism

Cellular/tissue tropism 

The range of cells/ tissues a virus can infect. 

• Specific: polioviruses - brain and spinal cord tissues 

• Non-specific: cytomegaloviruses – infect salivary glands, liver, lungs and even cross the placenta to infect foetal tissues 

Host range 

The range of species that a virus can infect 

• Limited: polioviruses – natural infection only seen in humans 

• Extensive: rabies – many warm blooded animals 

Determinants on viral specificity 

• Can the virus attach to the cell? 

• Receptor sites on host cells  

• Does the host cell have the machinery, enzymes and proteins required by this virus to replicate? 

• Can the replicated viruses be released from the host cell after they are produced? 

• Essential for spread of the virus to other cells in the host and to infect other host 

• Virus particles are metastable -  they exist in two forms: virion (out in environment) and infected cell 

General characteristics of viral infection

Adsorption 

1. Attachment to host cell 

Penetration 

1. Entry of virion or its nucleic acids into host cell 

Synthesis 

1. New nucleic acids, capsid protien, other viral compoents are produced using the host cell’s metabolic machinery 

Maturation 

1. Newly synthesised viral components are assembled => virion 

Release 

1. Release of newly synthesised virions 

1. Lysis of cell rupture (non-enveloped viruses) 

1. Disadvantage is cell is no longer able to create virus particle 

2. Budding (enveloped viruses) 

1. Cell can keep making virus particles 

Adsorbtion 

Requires virus and host cell recognition (host range & tropism) 

Non-enveloped: 

• Non-enveloped viruses have capsid proteins that function as attachment sites: 

• e.g. Rhinovirus canyon –adhesion protein binding 

 

Enveloped: 

• Enveloped viruses have glycoproteins (spike) proteins that extend outwards and bind to a receptor expressed on the surface of the host cells. 

• Ensures specificity for the host 

• e.g. SARS-CoV-2 spike protein binds the ACE2 receptor 

• These receptors have normal physiological functions but viruses take advantage of this to gain entry into the cell 

• ACE2 receptor – involved in the regulation of blood volume, electrolyte balance. 

penetration

Contents of the virus (particularly genome) must enter enter the cell. 

Non-eveloped viruses via endocytosis: 

• Endocytosis – virions bound to the plasma membrane are engulfed in pit-like structures and then internalised in a membrane 

Enveloped viruses can enter the cell via membrane fusion or endocytosis 

• Uncoating – enzymatic release of the viral genome from the protein coat (capsid/envelope) 

• Via proteolytic enzymes of either host or viral origin 

synthesis - replication

Regardless of the type of nucleic acid – in order to replicate, information in virus genome must be converted into mRNA (because they can be read by ribosome which than make proteins) 

what information is encoded in virus genome

MRNA relating to regulation of: 

• Viral protein sysnthesus (bust using host ribosomes) 

• Viral replication (usually requires viral protein or enzymes) 

• Virion assemblu 

Simple viruses with smaller genomes will use more host proteins: 

• More complex viruses with larger genomes often encode all the proteins and enzymes they need for genome replication 

The baltimore system 

I: dsDNA

II :ssDNA

III : RNA (+/-)

IV: RNA (+) eg SARS-CoV-2

V: RNA (-)

reverse transcriptase:

VI: ssRNA (+) eg HIV

VII: dsDNA

DNA virus replication (Group I & II) 

Remembering that the host cells that we’re focussing on will have double-stranded (ds) DNA genomes: 

• dsDNA (Baltimore Group I) viruses there are two phases: 

• Early transcription and translation – synthesis of key enzymes and proteins required for replication of viral DNA 

• Late transcription and translation – synthesis of structural proteins for capsid production 

• For ssDNA viruses (Group II), 

• first the complementary strand of DNA is synthesised --> dsDNA 

• The template for mRNA comes from this newly synthesised strand 

• Generally replication of the viral genome occurs in the host cell nucleus using host enzymes 

• Capsid and other proteins are sythesized in the cytoplasm with host cell enzymes 

RNA virus replication (group 3 to 6) 

• RNA viruses must encode for the enzymes that replicate viral RNA 

• The order of steps (transcription, translation, replication) required for replication of RNA viruses are dependent on the type of genome 

Sense vs antisense strand 

Sense (sometimes called +) strand 

• Can act as messenger RNA (mRNA) 

• MRNA is the template for protein synthesis 

Antisense (sometimes called -) strand 

• In viruses, serves as template for mRNA synthesis 

Group III (dsRNA viruses) 

Under normal, physiological conditions cells do not produce dsRNA 

Presence of dsRNA is associated with viral infection 

• Triggers immune responses  

Comprise of two strands of RNA 

• Two complementary RNA strands 

• The sense strand is used as the template for transcription --> proteins 

Group IV: ssRNA (sense RNA) 

• ssRNA (sense) genome acts as mRNA – viral proteins are made immediately after penetration and uncoating in the cytoplasm (e.g. SARS- CoV-2) 

• Sequence: 

• translation of viral replication proteins 

• Synthesise antisense (-; blue) RNA. This is used as a template for synthesising more copies of the sense (+) RNA genome 

• No nucleus involvement 

Group V: ssRNA (antisense) 

ssRNA (antisense) genome acts as a template for mRNA 

Requires viral enzyme 

Sequence 

• Use the antisense strand and viral enzymes (e.g., RNA- dependent RNA polymerase) to produce the sense strand (mRNA) 

• translation of viral replication proteins (cytoplasm) 

• Genome replication 

Group VI: ssRNA (sense) reverse transcription 

• Even though they has a sense ssRNA genome, replication occurs via a dsDNA intermediate 

• Sequence 

• Viral enzymes (e.g., reverse transcriptase) to produce dsDNA 

• Synthesise mRNA & replication of the viral genome 

• Translation of viral replication proteins (cytoplasm) 

Maturation of virion particles

Newly synthesised viral compoents are assembled into virion (new virus particles) 

• Involves both enzymes and proteins of viral and host origin 

• Viral nucleic acid encodes proteins and glycoportiens for new virions 

• Host cell machinery syntheisses envelope lipids and glycoproteins 

• Location of maturation is dependent on the type of virus 

Release

Key to the spread of infection – these newly synthesised virions must exit the cell to infect other hosts. 

Lysis (lytic) – occurs with both non- and enveloped viruses. 

• The plasma membrane lyses and progeny virions are released. 

• This kills the host cell  

•  e.g., poxvirus 

Exocytosis – occurs when the virus envelope is formed from one of the other intracellular organelles (e.g. nucleus, cytoplasmic reticulum or golgi). 

• Transported in vesicles that fuse with the plasma membrane to release the virions contained within  

• – e.g., varicella-zoster virus 

Shedding/budding – occurs when the virus buds through the host cell membrane as it is released from the cell  

• – e.g., Ebola 

Budding – enveloped viruses 

 

Enveloped viruses must acquire the envelope from a host membrane 

• Virion stimulates viral glycogen production 

• Viron buds through one of the cellular membranes (nuclear, endoplasmic reticulum, surface, or cell surafce 

Virus particles are metastable 

• Stable form= protects the genome 

• Unstable form=must release the genome (eg during penetration when the uncoating step happens) 

Requirements for successful infection --> disease 

Enough virus (virus specific 10 vs 10,000 virions 

1. Even though a single virus particle can initiate infection of host cell, not all viruses are successful 

Accessibility: 

1. to host and cells (host range) 

2. susceptible (adsorption) and 

3. permissive (cellular machinery can support viral replication). 

3. Ability to overcome immune (antiviral) defences 

Viral pathogenesis 

Disease following a viral infection (symptoms and effects of disease) 

Involves both the host and virus  

• Virus: effects of viral replication on the host 

• Eg cell lysis during release causes tissue damage as in ebola) 

• Host: immune respone to virus often are symptoms 

• Eg influenza causes fever and coughing 

• Infected host cell death by immune cells (eg cytotoxic T cells) 

.Site of viral entry

Skin is a strong barrier to infection 

• Largest orgain in the body, but the outer layer of skin are dead cells (viruses must infect living cell) 

• Very few viruses can infect skin unless there is an injiry or disruption (vectors like mozzies) 

Mucosal surfaces (layers of living cells, eg respiratory tract and GI tract) 

• Also additional barrier: eg pH 2.0 in stomach 

• But thet are lined by living cells -  good for viral enetry 

Site of viral entry- respiratory tract

• Mucosal surface that’s in constant contact with viruses from the environment --> one of the most common sites of infection  

• Usually, they come from the respiratory tracts of other infected individuals 

Example: site of viral entry – ACE2 receptor expression and SARS –CoV-2.  A CE2 receptor expression is very broad, took long time to find site of entry, understandings ite of entry can help explain symptoms and treatment 

Host defence against viral infection 

• Most of the consqeuences of viral infection (symptooms) are actually a result of the host response 

• A virus must overcome all of these barriers to infect a host and be able to infect other hosts.

host defense against pathogens: Anatomical barriers 

Physical: 

• skin 

Mucosal surfaces 

• Chemical: 

• pH stomach acid (1-2 vs tap water pH 6-8) 

*These are continuous barriers and to cause infection a virus must develop adaptive mechanisms 

intrinsc barriers against pathogen infection

Always present –provide immediate defense against viral infections often in conjunction with the innate immune system: 

RNA interference (RNAi) 

• Detection of foreign genomes (e.g., dsRNA) initiates responses to cleave and destroy 

• Molecular biology tool (CRISPR/Cas9 system - prokaryote) 

Autophagy 

• Detection of virus can trigger packaging of foreign viruses which are targeted for degradation within the cell 

Innate immunity - ALF 

immunity to infection that exists in an organism because of genetically determined characteristics. 

• Functiosn to destroy the virus 

• Doesn’t require a previous infection to be active 

• Activated within min/hrs 

Key players involved in response to virus 

• Pattern recognition receptors (PAMPs) 

• Recognise molecular patterns that indicate something is foreign 

•  eg foreign nucleic acids (TLR3 – dsRNA) 

Interferons (type 1) 

initially observed to be a substance that “interferes” with infection 

• Produced by both virus-infected cells and cells responding to signals from virus-infected cells 

• Reduces protein synthesis to kill viral infected cells 

• Induces gene expression in uninfected neighbouring cells 

• Including antiviral proteins – interfere with viral replication 

how do type 1 interferons work

Reduce the dissemination (spread) of infection 

• Stimulates immune cells to attack the virus infected cells 

• Causes the physiological effects associated with viral infections 

• “Flu-like” symptoms - fever, chills, nausea, etc  

• Prevent infection of additional cells, Rather than cure infected one

Cytopathic viruses

promote cell and tissue damage, which activates the innate immune response to produce cytokines (eg interferons) 

Consequence: 

• Increased blood flow 

• Increased cappilary permeability 

• Influx of immune cells 

• Tissue damage 

Cause 

• inflammation 

• Pain 

• Swelling 

• Heat 

• Redness 

• When large quantities of cytokines  enter the bloodstream it cause global effects (sleepiness, lethargy, muscle pain) 

  Noncytopathic viruses dont generate an effective innate respinse means poor adpative resposne means persistent infections 

Sentinel cells 

Constantly patrol the body looking for signs of change/anything foregn (eg dendritic cells, macrophasges 

• Link the innate and adaptive immune systens 

adaptive immunity

specific to pathogen, includes cell mediated immunity and antibody response

Antibody response 

• Antigen: substance recognised by the body as foreign 

• Antibody: protein produced in response to an antigen that is capable of binding specifically to that antigen 

 

• Immunoglobins (Ig) are the baic units of antibodies 

• Adaptive: 

• Antigen- binding domain important for specificity 

• Neutralising antibodies 

• Prevent a virus from infecting a cell 

• prevent entry into cells (e.g. IgA at mucosal surfaces) 

• Prevents virus spread by neutralising virus particles in the blood 

• Idea behind vaccination 

Cell mediated immunity 

• Important for clearing viral infections 

• Principal effectors cells are virus specific CD8+ cytotoxic T lymphocytes (CTLs) 

• Recognise viral antigens presented on the surface of infected cell 

• Lyse these target cell: 

• Transfer of cytoplasmic granules 

• Apoptosis 

This is a coordinated response that culminates in clearanc eof the virus, but keeps components that presist and can later respond, basis of vaccination 

initial host response to viral infections

Acute infection: 

• Relativily short duration with rapid recovery (eg influenza and noroviruses) 

Persistent infection: 

• Virus persists in body, can occur aftern an acute infection (potential caus eof long covid) 

Latent infection  

• – Virus persists in the host but is undetectable for a period of time prior to reactivation  

• (e.g. chickenpox & shingles – VCV (varicella zoster virus)) 

Chronic infection 

•  – Virus persists in the host and is detectable with disease present or absent 

• (e.g. hepatitis – HBV or HCV) 

Slow infections  

• – progressive accumulation of virus in the host. Can have long latent periods (e.g. AIDS – HIV) 

Asymptomatic 

• Infected and infectious but no obvious disease leads to new infections 

Epidemic 

• Comes from greek root ‘upon’+’people’ 

• Thucydides (460 BC–395 BCE) is thought to have first described an epidemic in writing to describe the Plague of Athens (430 BCE), which propagated from Egypt and Libya 

There was some understand of a new, emerging disease: 

• Was a single disease 

• Specific symptoms 

• Spread throughout a populationcausing excessive number of death 

• Epidemic happens within a specific population

Pandemic: 

happens globally, breaks out of a specific population and spreads beyond epidemic level (due to things like food shipping around the world, people flying around the wrld 

Most deadly pandemics 

• Most pandemics have been viral pandemic since the discovery of antibiotics in 1928 (penicillin) 

• The exception wcould be antimicrobial resistent (AMR) bacterial infections 

Epidemics and pandemics in aotearoa 

• Introduces European disease hit Māori populations hard 

• Between 1810 and 1840, 120,000 Māori deaths were caused by infectious disease 

• By the 1890s, Māori population size was about 40% of the pre-European contact population mostly due to disease 

questions to be prepared for future pandemics

• How do we know when a diesease will spread or when it will die or or become endemic? 

• How do we know which epidemic threshold is best? 

• What is the best way to stop the spread of a disease? 

• Why do certain populations get more sick? 

• Where should resources (test, vaccines, treatments) be sent first? 

These are answer by having good surveillance of disease forming good epidemiological models meaning we are able to predict the answer to this questions 

Epidemiology 

• The study of the spread of disease at the population

• Goes beyond the study of epidemics 

• Identify cuse of diseases 

• Determine extent of disease 

• Study natural history of disease 

• Evaluate public health interventions 

• Inform policy and decision making 

What can epidemiology tell us about the biology of a disease? 

1. If can determine pattern of exposure, can understand the cause of the disease 

2. If we understand the populations most affected, we can understand the potential for biological predispositions (eg genetic component?) 

3. Understand resistant populations can understand potential for resistance 

Epidemic and pandemic monitoring 

To prevent epidemics from goin pandemic, global health organisations why world health organisation (WHO) are monitoring outbreaks globally (countries report causes to these organisations) 

Patterns of exposure: eg legionnaires disease 

• in 1976, at the american legion convention in philadelphia, 182 guests developed a severe pneumonia and 29 died 

• Didn't spread person to person like covid, found it was limited to hotel where guest where staying, guests who stayed in a different hotel were unaffected 

• Pointed toward an environmental source inside that single building rather than person-to-person spread. 

• Risk rose with the amount of time spent in the hotel lobby and on the pavement beneath a street-level vent. Correlation between people who got sick and were hanging out around hotel lobby 

• Suggested airborne exposure emanating from the hotel itself. 

• No secondary transmission occurred among household contacts once attendees returned home 

• Reinforced that whatever the agent was, it was not readily contagious between people 

• CDC swabbed the hotels air conditioning system and isolated an unknown bacterium legionella pneumonia, that was foudn to cause the disease now called ‘legionnaires disease’ 

NZ pandemic plan 

• A crucial aspect of pandemic monitoring plan set up in NZ and around the world 

• Accurate reporting of sickness, death, determining cause of death 

• Tests for specific disease (know how many people infected) 

• Incidence and prevalence (know baseline expected incidence of disease is) 

• Infection rate (reproduction number) 

reproduction number (Ro)

• Reproduction number=average number of people that will be infected by an infected person 

• If its one (or close), may only infect one person, who then infects another person and so on, not likely to grow into an pandemic 

• If its much more than 1, the number can grow exponentially (each infected person infects more than 1 infected people etc) 

• This is assumed in a naive population with no immunity (eg due to no previous exposure) 

Basic vs effective reproductive numbers 

• the Basic Reproduction Number, or R0 (‘R naught’), is the average number of people infected by an infected person in a population with no immunity 

• The Effective Reproduction Number, or Re (sometimes shown as Rt), is the average number of people in a population who can be infected by an infected person at any given moment in time 

Re=Ro*(1-Pi)

Excess mortality 

• Sometimes the mortality of a disease is hard to calculate 

• To account for the toatal impact of a new disease, epidemiologists developed several methods to estimate the excess mortality 

• Eg flu is seasonal, peaks in cases in winter cause people are inside togetehr more, but what if more deaths than expected, need to know if seasonal or epidemic 

• Excess deaths= reported deaths – expected deaths 

Threshold for an epidemic 

• There are different ways to define a threshold for when an outbreak is called an epidemic (which could trigger a government response) 

Fixed incidence rate  

• For disease the known R0, eg measles epidemic threshold often set at1 case over million people per week 

Statistical rule 

• Epidemic if weekly cases > mean+2 standard deviations from past 5 years. Common for diseases like influenza 

Movin average 

• Epidemic declared if 2 consecutive weeks exceed a moving average threshold. 

Reproduction number (R>1) 

• If each case is infecting > 1 other person on average, the epidemic is growing. 

Expert judgement 

• In emerging disease, thresholds may be based on rapid risk assessment, not data history (eg legionnaires disease) 

Herd immunity 

Amount of people required in a population to stop a disease from spreading 

• Immunity can be gained by either through exposur to the disease of vaccines 

• Herd immunity acheived through vaccines leads to much less deaths  

• The herd immunity threshold, Pi (min percentage of population that need immunity to achieve herd immunity) is related to the R0 of the disease 

• Pi=1-1/R0  

SARS-CoV 

• Before 2002, we only knew of 2: 

• HCoV-229E and HCoV-Oc43 which were each responsible for a common cold 

• In 2002, a new coronavirus emerged that spread more quickly and was more deadly (770 deaths of about 8000 infections, fatality rate of 9%) 

• The disease was called “severe acute respiratory syndrome” (SARS) and the virus was SARS-CoV 

MERS-CoV 

• Then in 2012, another novel coronavirus emerged in the middle east and the disease was called Middle East Respiratory Syndrome (MERS), so the coronavirus was called MERS-CoV 

• This was determined to have jumped from camels, and most of the spread was camel-to-human (less human-to- human), could infect camels and camels acted as a resovior 

• Despite being less transmissible, of the 2500 confirmed infections, it caused 860 deaths (34% fatality rate) 

SARS-CoV-2

likely to have spilled over from bats

• 55% of cases documented in December 2019, were linked to Huanan Wholesale Seafood Market, a live animal market in the city of Wuhan, China 

• The most likely scenario is transmission occurred first from bats to an intermediary animal before being transmitted to humans 

• SARS-CoV spilled over from bats to civets to humans in 2002 

• MERS-CoV spilled over from bats to camels to humans in 2012 

SARS-CoV-2 Strain Evolution:  

Low Mutation Rate, but many opportunities to mutate (due to infectiousness) 

• SARS-CoV-2 has “proofreading” mechanisms to prevent errors in RNA replication, so it had a relatively low mutation rate 

• However, because it is so much more infectious, it has many more opportunities to mutate 

• therefore, many mutations occur because the number of opportunities to mutate (in each new infected person) outweighs the low mutation rate 

transmission of SARS-CoV-2

• SARS-CoV-2 is transmitted primarily in droplets in the air that an infected person or animal respires 

• The droplets land on the mucosal membrane (oral, nasal, eye) on a potential host and infect those epithelial cells first 

• Fomite transfer (droplets landing on surface then touching infected surfaces) also happens, but not thought o account for most transfer 

Symptoms and mortality of COVID 

• 4-5 days from infection to displaying symptoms 

Symptoms include:  

• Fever 

•  Cough 

• difficulty breathing, 

• Pneumonia (severe cases)  

• loss of taste and smell 

• Diarrhoea  

• loss of appetite 

• nausea 

Severe cases will lead to acute respiratory distress syndrome (ARDS), which happens in 42% of COVID cases that develop pneumonia 

• patients that develop ARDS have a mortality rate of 35-40%  

• ARDS may be the result of or trigger a “cytokine storm” (overcompensating immune response in lungs means reduced capacity for breathing) The overall mortality rate of COVID-19 is 1-2% 

Long covid 

• Long covid is a chronic condition that can last months after the acute covid infection 

• Long covid, like covid itself, can affect any organ and tissue that expresses the ACE2 receptor 

• This condition may not be unique t covid, other severe infections can lead to chronic fatigue syndrome (CFS) / myalgic encephalomyelitis

SARS-CoV-2 structure 

In the coronaviridae familiy, which all have: 

• Single-stranded, positive sense RNA genomes (+ssRNA), baltimore classification IV 

• Virions have envelopes with prominent spike proteins 

• Capsid is a nucleocapsid amd is helical, but wrapped up tight 

SARS-CoV-2 infection

• When SARS-CoV-2 virus attacks a potential host cell, it must bind to the Angiotensin-converting Enzyme-2 receptor (ACE2) 

• SARS-CoV-2 has a much higher affinity for this receptor than SAR-CoV 

Life cycle of SARS-CoV-2 

1. The Spike protein attaches to the ACE2 receptor and the virion is endocytosed or fuses to the membrane. 

• The exact mechanism of entry into the cell is still debated 

2.   

3.   

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5.   

NOT DONE, INCLUDE IMAGES AND INFO FROM SLIDES WHEN UPDATED

Mutations 

SARS-CoV-2 variants have mutations in the spike protein 

• Almost all major variants had mutations to the spike protein 

• These mutations increase the infection rate on the virions, and the virulence of the virus 

• Any time there is a mutation to make a virus more infectious, that variant becomes predominant, as it is more infections 

antigenic shift vs antigenic drift

Antigenic Drift = small changes in Viral genome, one mutation at a time 

Antigenic Shift = large changes in Viral Genome from combining large pieces of two virus 

Antigenic Shift Types: Reassortment and Recombination 

• SARS-SoV-2’s genome is one segment, making it harder for combination of two viral genomes to happen  

• Reassortment is mix and match of genetic materials 

• if two strains infect the same cell, but the genomes are spliced together during the replication step, that is Recombination 

• More rare than reassortment 

R0 gets higher with new variants 

• R0 values for SARS-CoV-2 variants: 

• Original: ~1.1 

• Delta: 3.2-8  

• Omicron: 8.2 (very infectious, lead to big wave in nz) 

Comparing morbidity across countrys (eg sweden and nz)

• Sweden had higher  number of deaths, but both had similar population and case levels.  

• Reason is due to when waves hit each population, and how much herd immunity already existed 

• Sweden got hit earlier, whiel nz later when already had may vaccine and some herd immunity (vaccination was main reason for this difference 

• Major spread of Covid occured in New Zealand in February 2022, after the vaccine immunized much of the population 

vaccination prevents death

• Covid-19 vaccines saved an estimated 20 million people in 2022 alone 

• This is because we already had vaccine by time more virulent omicron variant arrived 

• The scientists that paved the way for mRNA vaccines won the Nobel Prize in 2023 

Reassortment (antigenic shift)

In the case of influenza: 

• Influenza genome is in 8 segments, and it is relativly easy for parts of a genome to mix and match 

• Parts are repackaged up into different virion, eg with 6 of 8 segments of one virus match with 2 of 8 segments of another virus combine to join together to make a new virus 

• When segments are replicated when 2 virus strains infect the same cell and they are assembled together, this is Reassortment 

• More common, viruses have to have mutiple segments, viruses can evolve to do this 

recombination (antigenic shift)

• SARS-SoV-2’s genome is one segment, making it harder for combination of two viral genomes to happen 

• If two strains infect the same cell, but the genomes are spliced together during the replication step, that is Recombination 

• Rare, happens in viruses whose genome is only one segment, happens randomly 

HIV= virus, AIDS=disease caused by the virus 

Gay –related immune deficiency (GRID) 

• Late 1970’s and early 1980’s: gay men started dying with Kaposi’s sarcoma and Pneumocystic carinii   

• Pneumonia—both diseases thatnever happen in young andotherwiase healthy adults 

• It became known as a gay disease or “the gay cancer” and was even officially called “Gay-Related Immune Deficiecy” (GRID) before it was discovered to affect non-gay people 

Named “acquired immunodeficiency syndrome (AIDS) 

• After the tell-tale signs of AIDS were discovered in people that received blood transfusions, children born to infected mothers, drug users that shared needles, and in straight women, it became clear it was disease anyone could get 

• It was then named AIDS, but the fact that gay men were the primary population infected, meant that resources and media attention would be delayed in offered sympathy and help 

• Found specific to blood transmission and mucus membranes (excluding respiratory membranes) 

HIV transmission pathways 

• blood transfusion

• mother to child

• unprotected intercourse

• contaminated needles

Largely infected gay men due to higher rates of unprotected sex since didn’t have to worry about pregnancy 

Cause of death (HIV/AIDS)

• As the immune system weakens, HIV eventually induced AIDS, and patients develop fever, headache, rash, sore throat 

• People who develop AIDS often die of normally preventable infections, such as the virus that causes the common cold 

• Patients often developed rare cancers that only afflict extremely immunocompromised people, like certain lymphomas and Kaposi’s sarcoma 

• Presents intially as a cold, then goes away and comes back years later to cause immmune system to collapse. 

HIV (human immunodeficiency virus) 

• HIV is Baltimore Class VI, which is retroviruses 

• Retroviruses are defined by their ability to integrate their viral genome into the host cell’s genome, making them hard for host cells to detect and eradicate 

All retroviruses must carry two enzymes in the capsid withthem for this integration to occur: 

• Integrase 

• Reverse Transcriptase 

HIV binds CD4 receptors 

• CD4 recpetors are found on helper T cells, macrophages, dendritic cells (all types of white blood cells) and also astrocytes (brain cells that act as immune cells ) 

• Once bound, the viral envelope fuses with the plasma membrane of the cell, and the capsid and other viral proteins are released into the cytoplasm of the cell 

HIV to acute HIV syndrome and AIDS thresholds

acute 

• CD4 drops initially, but immune system fights back and HIV viral loads are reduced 

chronic 

• Slowly kills CD4 cells over time and immune system depletes 

AIDS 

• <400 CD4 or aids defining illness, collapse of immune system 

Retrovirus life cycle 

Reverse transcriptase creates new DNA with virus RNA into it, creating proviral DNA 

Proviral DNA is integrated directly into host DNA, makes it very difficult to treat or produce vaccine as very difficult for immune system to find infected cells 

May be able to target vaccines and treatment to block action of reverse transcriptase

HIV vs. SARS-CoV-2 Viral Life Cycle 

• Both SARS-CoV-2 & HIV: +ssRNA genome, envelope, budding 

• HIV get converted to DNA and integrates into genome, can remain ‘hidden’ 

• SARS-SoV-2 produces new viral genomes and proteins immediately in cytoplasm of host cell 

HIV causes progressive loses of helper T cells 

• Infected CD4+ T Lymphocytes (Helper T cells) are eliminated with a half-life of 2-4 days (50% of infected cells die in 2-4 days) 

CD4+ T lymphocytes (Helper T) cells die either from: 

• The cytotoxic HIV particles killing the cell 

• Lysing by cytotoxic T lymphocytes 

• The HIV virus produces proteins that prevent the maturation and replacement of new helper T Cells