Enveloped Segmented SS RNA Viruses (6/10)

Zhou Lecture 5 (Lecture 23)

Orthomyxoviruses: Influenza

spherical

lipoprotein envelopes with spikes

what are the spike proteins on Influenza?

Hemagglutinin (HA)

• bind to cell receptors, cause RBC aggregation

• different antigenic types

• functions to adsorb virus to host cells: infection

Neuraminidase (NA)

• hydrolyze protective mucous coating of respiratory tract

• keep viruses from sticking together

• functions to facilitate virus release

What are the genomic variations of influenza? Why are there repeated epidemics?

antigenic shift: major change in HA (H1-16) or NA (N1-9)

antigenic drift: minor change, point mutations

recombination between human, avian or animal strains

what was the 2009 Influenza A pandemic?

4 H1N1 flu viruses:

• North America swine flu

• North AMerica avian flu

• Human flu

• Asia/Europe swine flu

Pathogenesis of Influenza

Infection limited to upper respiratory tract

NA binds to the mucoproteins of resp tract

death of ciliated epithelial cells, loss of resp epithelium, severe inflamm/irritation

Symptoms and death of influenza

symptoms: fever, headache, pharyngeal pain, sob, cough, myalgia

death: invasion of lower resp tract by staphylococcus, pneumococcus, streptococcus, pneumonia

SEQ cell invasion and disruption by influenza virus

adsorption

(-) sense RNA moves into nucleus, transcribed into mRNA

mRNA translated red, (+) Sense RNA

(+) Sense RNA used to synth gp spikes inserted into host membrane and (-) Sense RNA molecules for assembly

release of mature virus occurs when viral part gather at cell membrane and budded off with envelope containing spikes

epidemiology of influenza A

acute, highly contagious resp infection

three types of influenza: type A most virulent

repeated epidemic

mortality rate 0.1% elders and children

transmission of influenza A

inhalation of virus-laden aersols, facilitated by crowding and poor ventilation

H1N1 symptoms

(most to least)

fever > cough > sob > fatigue > chills > mylagias, rhinorrhea > sore throat, headache > vomiting > wheezing/diarrhea

high risk groups <2 or >65 yrs, pregnant, AIDs

more severe symptoms in younger people

what are emergency warning signs of influenza A in children?

uncontrolled breathing

bluish skin color

not drinking enough fluids, or not waking up/interacting

being irritable, child does not want to be held

flu-like symptoms improve but return with fever and worse cough

fever with rash

what are emergency warning signs of influenza A in adults?

difficulty breathing, sob

pain/pressure in chest/abdomen

sudden dizziness

confusion

severe/persistent vomiting

Treatment of H1N1 infection

Drugs:

• Tamiflu, Relenza — may have allergic rxns, n + v

• neuraminidase inhibitors

• inhibit A and B, only used with high risk groups

Vaccine:

• shots: inactivated viruses

• nasal spray: weakened live viruses

• should not: allergy to eggs/flu vax, kids <6 mo, with fever

What should we expect after H1N1 vaccination

flu shot: soreness, redness at injection site, low grade fever, aching

nasal spray: mild cold symptoms

very safe: no severe deleterious fx

types of paramyxoviriuses

parainfluenza viruses and mumps

morbilllivirus (measles)

pneumovirus (resp syncytial virus)

cell fusion to form multinucleate giant cells

describe the parainfluenza virus (transmission, symptoms, therapy)

spread by droplets and respiratory secretions

most children infected by 6

symptoms: cold, bronchitis, bronchopneumonia, croup

no effective therapy

What is mumps?

paramyxovirus/epidemic parotitis

target parotid salivary glands

symptoms: fever, nasal discharge, muscle pain, malaise, inflammation of the salivary glands

complete recovery: <15 yrs

40% subclinical

lasting immunity, no carrier state

immunization works well

what is measles?

invades mucosal lining of respiratory tract

contagious, humans are only reservoirs

symptoms: sore throat, dry dough, HA, rash, lymphadenitis, conjunctivitis, fever

spread: resp aersols

prevention: immunization

What are 3 types of rubiviruses?

rubella: togavirus, non-segmented, ss RNA virus with loose envelope

Postnatal rubell: malaise, fever, sore throat, lymphadenopathy, rash; adults have mild joint inflamm, pain

Congenital rubella: miscarriage, multiple permanent defects in newborn (cardiac abnormal, ocular lesions, deaf, mental retard)

there is vaccination

What is rhabdowvirus? how is transmitted? when do symptoms appear?

rabies: acute, paralytic, death

rabies virus: rhabdovirus family, bullet shaped, helical symmetry

transmission: saliva via bite would, travel through nerve trunks to brain

symptoms appear when it hits the brain

100% fatal

who is the primary reservoir of rabies? how is it spread?

wild mammals: wolves, foxes, skunks, raccoons

bats > skunks (100-1kx more viruses in saliva than dogs) > humans

bats spread infections to dogs and cats

spread by bites, scratches, inhalation of droplets

what are forms of rabies?

furious rabies: excited, no fear

dumb rabies: paralysis and death

humans: hydrophobia

how can you prevent/treat rabies?

incubation period: 2-6 weeks

prevention: control stray drogs (immunization/eliminate reservoir

if bitten by dog: extensively wash would, disinfect, infusion of human rabies immune globulin and full course of vaccine, examine dog for infection

what is polliomyeltisi?

infantile paralysis: poliovirus

• acute infectious

• affects brain and spinal cord

• pico

• RNA genome

Paralysis due to destruction of motoro neurons

vaccine aval

what are the 4 types of poliovirus infection?

silent infection

abortive

nonparalytic

paralytic

What is ebola virus?

filovirus: enveloped, non-segmented, negative ss RNA

high fatality, many bleed to death

no specific treatment

outbreak 2014: fruit bats

pathogenesis of ebola

direct infection of tissues, immune dysregulation

hypovolemia and vascular collapse

• electrolyte abnormalities

• multi-organ failure, septic shock

disseminated intravascular coagulation (DIC) and coagulopathy

How can we recognize ebola?

acute onset: 8-10d after exposed

S&S:

• initial: fever, chills, myalgias, malaise, anorexia

• 5 days: GI irritation (n and v, diarrhea)

• HA, conjunctivitis, jiccups, rash, chest pain, sob, confusion, seizures

• hemorrhagic symptoms

• Other: malaria, typhoid fever, meningococcemia, lassa fever, bacterial infections

What are the clinical features of ebola?

nonspecific early symptoms can progress to: hypovolemic shock, multi organ failure, hemorrhagic disease, death

severe cases require IV and electrolyte management to decrease fatality

non fatal: improve 6-11d after onset

Diagnosis and treatment of ebola

Diagnosis: rt-PCR

Therapy: convalescent serum

Vaccines:

• attenuated vesicular stomatitis virus with EBola virus gene inserted

• chimpanzee derived adenovirus with ebola virus gene inserted

what are some therapeutic medications of ebola?

Zmapp: 3 chuimeric human mouse mabs

Brincidofovir: oral nucleotide analogue with antiviral activity

Favipiravir: oral RNA dependent RNA polymerase inhibitor

What are arboviruses?

spread through arthropod vectors

chief vectors: blood sucking arthropods; mosquitoes, ticks, flites, gnats

family: flaviridae, 11kb, ± ssRNA enveloped

mostly mild, but may cause encephalitis and hemorrhagic fevers

WW

Give examples of arboviruses affecting the US

colorado tick fever: rocky mountain area

wester equine encephalitis: carried by mosquitoes

easter equine encephalitis: carried by mosquitoes, appears in horses and caged birds, high fatality rate

St. Louis encephalitis: west and south states, inapparent infection

What is west nile encephalitis?

family: flaviviridae

asymptomatic or mild fever

severe/fatal infection in elderly: high fever, HA, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle wekeness, vision loss, numbness and paralysis

spread by Culex moquitoes

prevention: surveillance for virus in birds and mosquitoes

• control with pesticides

What is Yellow and Dengue fever?

carried by mosquitoes, have RNA genome, genus Flavivirius

yellow fever: 2-3 day fever, excessive bleeding, black vomit

• Western Hemisphere

dengue: ss + stranded RNA virus, mild

• breakbone fever: intense muscle and joint pain

• SEA, S and C America, Caribbean and Mexico

What is coronavirus?

spikes on envelopes, solar corona

animals: epidemic respiratory, enteric, neurological disease in pigs, dogs, cats, poultry

common cold in humans

SARS/Covid: severe acute respiratory syndrome

Describe the structure of coronavirus

Spike(S) gp

• receptor binding, membrane fusion

• targeted by host neutralizing antibodies

Envelope (E)

• virus infectivity

Matrix (M) gp

• abundant structural protein

• interacts w E to form viral envelope

What is SARS?

severe acute respiratory syndrome

symptoms: high fever, HA and body, 2-7d, dry cough, pneumonia w severe lung damage

SARS-CoV

Asia

Transmission: close contact, respiratory droplets, contaminated surface

Origin: resturant worker working with exotic wild animals as food

• human viruses: 29nt deletion, homologous(humans and animals)

Describe the structure of SARA-CoV-2

spike S1 and S2

Nucleocapsid N

Membrane M

Envelope E

ssRNA (+)

highly identical to bat coronavirus

Clinical symptoms of COVID 19

common signs: loss of taste or smell, running nose

more severe: difficulty breathing, muscle aches, chest pain, pink eye

symptoms appear 2-14 days after exposure

Do elders with underlying conditions have higher risk of death from covid?

Yes: 80+ with heart, pulmonary, obesity, weak immunity, diabetes, high bp

main pathology to death: difficulty breathing, organ failure, heart problems, blood clotting, acute kidney injury and secondary infections

List the types of COVID vaccines

inactivated/attenuated CoV-2 virus: from China and India

viral vector: make viral proteins, carry covid proteins on surface

genetic: viral mRNA, DNA (pfizer, moderna)

protein vaccines

currently being developed: nasal, dried vaccines for high temp transport

summary of COVID Vaccine and treatment

What are the hepatitis viruses?

Hepatitis viruses are a group of liver-infecting viruses (A–E) covered in the earlier portion of the lecture series.

Does HBV contain DNA or RNA?Dane’s particle? Infectious? 22-nm particles?

HBV contains DNA.

The Dane particle is the infectious form of HBV; the 22-nm spheres are non-infectious surface antigen particles.

What is the evidence that HBV causes liver cancer?

Chronic HBV infection leads to cirrhosis and greatly increases risk of hepatocellular carcinoma.

Influenza viruses: function of HA and NA?

HA mediates viral attachment and entry; NA helps the virus exit the cell and prevents viral clumping.

HA mediates viral attachment and entry; NA helps the virus exit the cell and prevents viral clumping.

Why repeated epidemics? Antigenic shift vs. antigenic drift?

Drift = small mutations causing yearly epidemics; shift = major HA/NA recombination causing pandemics.

What causes measles? Morbillivirus?

Measles is caused by Morbillivirus, a paramyxovirus.

What causes Rabies? Rhabdoviruses?

Rabies is caused by a Rhabdovirus, a bullet-shaped RNA virus spread mainly by bites.

What is the major pathology for poliovirus?

Poliovirus destroys motor neurons, leading to paralytic disease.

Mumps?

Mumps is a paramyxovirus infection that targets the parotid glands and causes swelling, fever, and malaise.

What causes Ebola virus?

Ebola is caused by a Filovirus, an enveloped, non-segmented, negative-sense RNA virus.

What are the major Ebola symptoms?

Ebola causes fever, severe GI symptoms, immune collapse, hemorrhage, hypovolemic shock, and multi-organ failure.

Where did Ebola virus come from?

The 2014 outbreak likely began with a 2-year-old boy in Guinea, with fruit bats as the reservoir.

What is SARS? Symptoms?

SARS is Severe Acute Respiratory Syndrome caused by SARS-CoV and produces high fever, dry cough, and pneumonia.

What is COVID-19?

COVID-19 is the respiratory disease caused by SARS-CoV-2, ranging from mild illness to severe pneumonia and death.

What is SARS-CoV-2?

SARS-CoV-2 is a coronavirus 79.6% identical to SARS-CoV and 96% identical to a bat coronavirus.

What are the major symptoms of COVID-19?

Common symptoms include fever, chills, cough, fatigue, loss of taste/smell; severe cases include breathing difficulty and chest pain.

Why do people die from COVID-19?

Death is caused by respiratory failure, organ failure, clotting disorders, cardiac problems, kidney injury, or secondary infections.

Are young people ok to get infected? Why or why not?

Young people have very low mortality (~0.2%) but can still develop severe disease and spread infection to others.

What are the major types of COVID-19 vaccines?

The main types are inactivated/attenuated, viral vector, genetic (mRNA/DNA), and protein-based vaccines.

What public health measures are critical for controlling the pandemic?

Vaccination, masking, variant monitoring, and reducing transmission through public health interventions