Virology III Viral Genomes

What type of genome do Picornaviruses have?

ssRNA, + (sense) strand (treated as if it's mRNA)

Why is a + strand RNA virus directly infectious?

Because it is treated as mRNA – host ribosomes can translate it immediately upon entry (no need to bring an RNA polymerase!)

Does Picornavirus have an envelope or naked capsid?

Naked capsid (no envelope)

What is the shape of the Picornavirus capsid?

Icosahedral with symmetrical subunits

Where does Picornavirus replication occur in the host cell?

Cytoplasm

Can Enterovirus survive at low pH (pH 3-9) ?

YES (pH 3-9)

How is Enterovirus transmitted?

Fecal-oral and respiratory

At what temperature does Enterovirus grow best?

Above 33°C

Does Enterovirus have a specific tissue preference?

Depends on the virus (different enteroviruses target different tissues)

Can Rhinovirus withstand low pH?

NO

How is Rhinovirus transmitted?

Respiratory and fomites (contaminated surfaces)

At what temperature does Rhinovirus grow best?

< 33°C (prefers cooler temperatures of the upper respiratory tract)

What tissue does Rhinovirus infect?

Respiratory tract

What determines which cells a Picornavirus (Enterovirus/Rhinovirus) can infect?

Specific tissue receptors on the cell surface (virus-receptor binding is highly specific)

How do Picornaviruses take over the host cell?

1. Inhibit cellular RNA and protein synthesis (shut down host production)

2. Viral mRNAs out-compete cellular mRNA (viral messages win the race)

What advantage do viral mRNAs have over cellular mRNAs during Picornavirus infection?

Viral mRNAs out-compete cellular mRNA for the host's translation machinery

How is the + strand RNA genome of a Picornavirus translated?

Translated into one long polypeptide (polyprotein) → then cleaved into individual proteins (structural, enzymatic, etc.)

How long does it take to complete Picornavirus protein synthesis?

10-15 minutes (very fast!)

Why is the Picornavirus + strand RNA immediately infectious?

Because it is treated as mRNA – host ribosomes can translate it directly without any viral enzymes needed first

What are the three main types of Enteroviruses?

Poliovirus, Coxsackievirus, Echovirus

How are Enteroviruses transmitted?

Fecal-oral and respiratory droplets

What are the three portals of entry for Enteroviruses?

1. Intestinal mucosa

2. Respiratory mucosa

3. Oropharynx

Where do Enteroviruses first multiply after entry?

Lymph nodes and tonsils

Where do Enteroviruses spread after initial replication?

Reticuloendothelial system → liver, spleen, lymphoid tissue

How are Enteroviruses shed from the body?

1. Feces (into environment)

2. Oropharynx (respiratory droplets)

What type of effect do Enteroviruses have on cells?

Cytolytic (destroy tissue)

What factors determine the pathology of an Enterovirus infection?

• Serotype

• Dose

• Tissue tropism

• Portal of entry

• Age

• State of health

Do Enteroviruses generally cause GI disease?

NO – DO NOT generally cause GI disease (important exception!)

What is the protective immune response against Enteroviruses?

Antibodies (IgA) – mucosal immunity

How does Poliovirus enter the body?

GI tract (contaminated water) OR respiratory tract

What are the 4 levels of disease severity for Poliovirus infection?

1. Asymptomatic

2. Abortive poliomyelitis (minor)

3. Non-paralytic polio

4. Paralytic polio (major illness)

In asymptomatic Poliovirus infection, where is the virus restricted?

Gut or oropharynx (no spread beyond entry sites)

What are the symptoms of abortive poliomyelitis?

Fever, headache, malaise (minor illness)

Is abortive poliomyelitis infectious?

YES – infectious!

What complication can non-paralytic polio cause?

Aseptic" meningitis (viral meningitis)

What does "aseptic" meningitis mean?

Meningitis caused by virus (not bacteria) – so no bacteria seen on culture

How does Poliovirus reach the spinal cord in paralytic polio?

From blood or skeletal muscle → travels to spinal cord → innervating nerves → brain

What happens to neurons in paralytic polio?

Neurons are destroyed (cytolytic!)

What determines the severity of paralysis in paralytic polio?

Extent of nerve damage (more damage = more severe paralysis)

How many wild strains of Poliovirus exist?

Three (Types 1, 2, and 3)

Put the Poliovirus disease spectrum in order from mildest to most severe

Asymptomatic (virus restricted to gut/oropharynx)

Abortive poliomyelitis (fever, headache, malaise – infectious)

Non-paralytic polio (aseptic meningitis)

Paralytic polio (neurons destroyed → paralysis)

What are the two types of polio vaccines?

1. Inactivated virus (Salk, 1955)

2. Oral live attenuated virus (Sabin) – CURRENT VACCINE

What are the 3 advantages of the Sabin (oral) vaccine over the Salk vaccine?

1. Less expensive

2. Easier to administer (oral vs. injection)

3. Lifelong immunity

What happens to attenuated viruses in the Sabin vaccine?

They grow but are altered and do NOT cause infection

What unique feature does the oral Sabin vaccine have regarding viral shedding?

Attenuated virus is shed – which IMMUNIZES OTHERS! (passive immunization of contacts)

What is herd immunity?

When enough people get immunized → difficult for virus to spread → creates protection for unvaccinated individuals

What percentage of the population needs to be vaccinated to achieve herd immunity for Polio?

80% of the population

What is the most common viral infection in humans?

Rhinovirus

What are the characteristics of Rhinovirus? (size, effect, envelope)

One of the smallest viruses, lytic, non-enveloped

How many different serotypes of Rhinovirus exist?

200 different serotypes

Can you get lifelong immunity to Rhinovirus?

NO – immunity is rare (too many serotypes!)

How does Rhinovirus enter the body?

Eyes, mouth, nose

Where does Rhinovirus replicate?

Upper respiratory tract (NOT GI tract)

Why doesn't Rhinovirus infect the GI tract?

It is acid labile (cannot survive stomach acid)

What temperature does Rhinovirus grow best at?

33°C (cooler temperature of the upper respiratory tract)

How many infectious particles are needed to start a Rhinovirus infection?

1 infectious particle is sufficient!

What is the progression of symptoms in a Rhinovirus infection?

Sneezing → Runny nose → Obstruction → Cough

Is there a vaccine for Rhinovirus?

NO – not a good candidate because there are too many serotypes (200!)

Are experimental drugs and over-the-counter treatments reliable for Rhinovirus?

NO – not proven reliable

What are ways to prevent Rhinovirus?

• Cover your mouth

• Wash your hands

• Disinfect surfaces

What family does Influenza belong to?

Orthomyxovirus

Does Influenza have an envelope?

YES – ENVELOPED

What type of genome does Influenza have?

ssRNA negative (anti-sense) strand

What unique ability does Influenza's segmented genome allow?

Reassortment – segments can shuffle and mutate → FORMS NEW STRAINS

Why is reassortment dangerous for humans?

It creates new strains that our immune system may not recognize (antigenic shift)

How many types of Influenza infect humans?

Three – Influenza A, B, and C

How is Influenza spread?

Respiratory droplets and on surfaces

How long can Influenza survive on surfaces?

Up to 1 day

What specific cells does Influenza infect and kill?

Ciliated cells on the respiratory tract

Why is killing ciliated cells significant?

Ciliated cells are the 1st line of defense of the respiratory tract (they sweep out mucus and debris)

What are the two major envelope proteins of Influenza A?

1. Hemagglutinin (HA)

2. Neuraminidase (NA)

What is the function of hemagglutinin?

Attachment and fusion of envelope

What is the function of neuraminidase?

Mucus hydrolysis and release from host cell

How are Influenza viruses named?

Based on the two envelope proteins (Type A/B/C followed by H and N subtypes)

How many types of hemagglutinin (H) exist?

16 types (H1, H2, etc.)

How many types of neuraminidase (N) exist?

9 types (N1, N2, etc.)

What is an example of a formal Influenza name?

A / Spanish / H1N1
(Type / Name / H#N#)

Where is the Influenza nucleocapsid injected?

Into the cytoplasm

What is the replication pathway for Influenza RNA?

Anti-sense (- strand RNA) → + strand (mRNA) → protein

What enzyme must Influenza encode because it has a negative-sense RNA genome?

RNA dependent-RNA polymerase (host cells don't have this enzyme!)

How long does it take for Influenza to replicate and release new virions?

8 hours

What was the 2009 pandemic virus?

Swine flu – Influenza A (different H and N than traditional H1N1)

What conditions allow a new pandemic strain of Influenza to emerge?

1. Co-infection of a host with 2 or more Influenza strains

2. Reassortment of genes creates a new strain

What is reassortment?

The shuffling of gene segments when a host is co-infected with two or more Influenza strains → creates a new strain with a novel combination of H and N

Why is reassortment more dangerous than mutation (drift)?

Reassortment creates a completely new combination of H and N that no one has immunity to, whereas drift is just small changes to existing strains

What is the first clue for diagnosing Influenza?

Note the season the illness occurs! (Influenza is seasonal)

What are the common symptoms of Influenza?

Fever, malaise, chills, aches (systemic symptoms)

What are the 3 methods used for Influenza culture (though not often done)?

1. Cytopathology

2. Genetics

3. Serology

What is the RAPID INFLUENZA DIAGNOSTIC TEST and how long does it take?

A rapid test that gives results in 15 minutes

Can the flu vaccine cause the flu?

NO – VACCINE CANNOT CAUSE FLU!

What type of immunity does the flu vaccine provide?

Antibody-mediated protection (specific to H and N types)

Which flu types are included in the vaccine?

Influenza A (specific H/N types like H1N1, H2N3, etc.) AND Type B

What are the two types of flu vaccines?

1. Killed viral vaccine (injectable)

2. Live/attenuated vaccine (nasal spray – FluMist)

What family does Measles belong to?

Paramyxoviridae

What genera does Measles belong to?

Morbillivirus

How many serotypes of Measles exist?

One serotype

Does Measles have an envelope?

YES – Enveloped

What is the shape of the Measles nucleocapsid?

Helical

What type of genome does Measles have?

Negative (-) ssRNA (not segmented)

What enzyme must Measles encode?

RNA-dependent RNA polymerase (host cells don't have this)