Viral respiratory infections Flashcards

1
Q

___ is a +ve sense, non-enveloped ssRNA virus (belongs to Picornavirus family) that mainly causes the common cold

A

Rhinovirus

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2
Q

Describe the replication cycle of rhinovirus

A

Basically the same as any other non-enveloped rna virus. Since its +ve sense, no need to bring its own rna polymerase, and two important things are: Rhinovirus exits the cell via lysis (makes sense coz its naked so it doesn’t need an envelope) which causes an inflammatory response and has an icosahedral capsid which is important for vaccine design/lack thereof

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3
Q

Where in the URT does Rhinovirus replicate?

Which component of the immune system is involved in fighting Rhinovirus infection?

A

In nasal epithelium

Only innate immunity involved

**also know that viral titers peak within 2 days and are gone by day 5 so I guess that’s when you’re symptomatic, and symptoms happen a day after inoculation**

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4
Q

What are the groups of Rhinovirus and which one is the most clinically important?

A

Groups A, B and C

**Group A most clinically important**

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5
Q

___ is a -ve sense, enveloped ssRNA virus that, like Rhinovirus, primarily causes URI but can also cause viral pneumonia in severe cases

A

Influenza virus

**Recall that the Influenza virus belongs to the Orthomyxovirus family and has 8 segments (the O in BOAR)**

**remember also that this family replicates in the NUCLEUS unlike the other rna viruses**

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6
Q

Describe the structure of the flu virus. Which 2 proteins are on the viral envelope that are crucial for its function? ___ is also an envelope protein-channel that mediates viral uncoating

A

Envelope is studded with various proteins including hemagglutinin, and neuraminidase (HA and NA). Envelope also has the M2 protein which is a channel that mediates viral uncoating

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7
Q

How is flu transmitted?

Describe the influenza vius replication cycle

A

HA binds to sialic acid which allows for endocytosis of viral capsid

Viral genome goes to nucleus for transcription, m-rna exported out to cytoplasm for translation and proteins meet and assemble at plasma membrane.

Resulting virion exits via budding, unlike Rhinovirus which leaves by lysis

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8
Q

There are currently 3 drugs used to treat flu. Name them (hint: Amanda, Tammie and a Balo-rena)

A

Amantadine (Symmetrel) blocks M2 (so it blocks uncoating mediated by acidification of the endosome) – all strains currently resistant to this

Oseltamivir (Tamiflu) blocks neuraminidase (which cleaves sialic acid on the membrane from which the virion is budding so it can actually leave the cell)

Baloxavir/Xofluza – blocks the virus’ cap snatching process (so basically the virus steals a 5’ cap from the host m-rna and places it on its own m-rna so the drug blocks the virus’ cap-dependent endonuclease)

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9
Q

Explain the difference between antigenic drift and antigenic shift

A

Antigenic drift: point mutations in the viral genome that results in variations in HA and NA proteins – so that’s why we need a new vaccine every year

Antigenic shift: when segments are shared (and recombine) between different spp of influenza virus

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10
Q

Describe the current flu vaccines that are out there

A

There’s a standard inactivated vaccine from various strains, then a live attenuated vaccine made from recombinant HA and NA proteins from same genomic backbone

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11
Q

Contrast the 2 theories behind a universal flu vaccine

A

Headless HA theory: you remove the head of the HA protein which is highly variable and you make antibodies against the stalk, which doesn’t change as much

Stalk - diff head antibodies: you make antibodies to one stalk type you also boost with antibodies against same stalk but different HA heads

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12
Q

Describe the characterstics of parainfluenza virus

A

-ve sense ssRNA virus; member of the Paramyxovirus family; enveloped

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13
Q

What is a key difference betweent the replication cycles of flu and paraflu?

Parainfluenza most commonly causes __ and __

A

Difference between Paraflu and flu is that this has a Fusion surface protein that allows it to fuse with the plasma membrane and release its genome that way without the endosome acidification that’s required by flu

Parainfluenza most commonly causes Croup and bronciolitis

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14
Q

Describe the replication cycle of parainfluenza virus

A

Effectively the same as other rna viruses

*virus fuses with membrane via the F protein at NEUTRAL pH, and replication takes place in the CYTOPLASM, unlike flu*

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15
Q

How is parainfluenza virus transmitted?

Where does the virus replicate (hint: this is why infants are acutely susceptible to infection)

A

PIV is transmitted via droplet transmission/person-person contact

It replicates in ciliated epithelial cells, and infants are more suscpetible b/c they don’t make enough mucus/layer is more fragile and their cilia are less developed

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16
Q

Which virus is the leading cause of serious pediatric viral respiratory infections worldwide? What two conditions does this virus cause?

A

Respiratory syncytial virus; causes pneumonia and bronchiolitis

**note that HMV - human metapneumovirus - is second most important respiratory virus worldwide after RSV (in kids!!)**

17
Q

Describe the characteristics of RSV (and HMV)

A

They’re both -ve sense ssRNA, enveloped viruses in the Paramyxovirus family

18
Q

Describe the replication cycles of RSV and HMV

Why is RSV called RSV?

A

Both the same as other rna viruses: replicate in the cytoplasm. Difference: binds to cells using the G protein but fuses to membrane with F protein

Basically, cells neighboring the virally infected cell will also have the virus’ receptor and the fusion protein so somehow that can causes the cells to stick together and form syncytia, which are generally weaker, burst more easily and can lead to a more serious inflammatory response/disease

19
Q

Describe the characteristics and replication cycle of Adenovirus

A

F fibers on the virus dissociate from its surface which allows for new proteins to bind inside and traffic the viral genome to replicate in the nucleus

**its a ds dna virus, non-enveloped (the A in DNA viruses are HHAPPPPy)

20
Q

Which Adenovirus strains are more commonly ass’d with mild disease vs more severe illness?

A

Adenovirus 1 and 2 are commonly associated with mild illness

Adenovirus 7 linked to severe disease

**causes a febrile, mild URI type disease in kids but also in young adults**

21
Q

24 year old medical student began to have a sore throat in the morning and noticed slowly increasing nasal stuffiness, runny nose, and sneezing later in the day. The next day the symptoms were worse. She takes her temperature, finds no fever, but feels “out of energy”. What viruses are on your differential?

A

Syndrome: Common cold **note that common cold symptoms are going to be limited to the upper respiratory tract**

Rhinovirus

Coronavirus

Adenovirus

22
Q

Describe the pathogenesis of rhinovirus

A

**need to think about where the bug goes >> what symptoms can come from that**

Likes to grow in cooler temps (hence in URI where temp is cooler than body temp)

Attaches to host cell via ICAM1

Rhinitis and sore throat are mediated by increase in bradykinin (also influx of PMN)

Limited cytolysis (so this is not an aggressive infection)

23
Q

How can you tell that an infection is the common cold (Rhinovirus) as opposed to any other common cold virus

A

Typically NO fever and remember the symptoms are more in the face (sneezing, runny nose, nasal obstruction, sore throat, headache, malaise)

Also, seasonality: peaks in Fall (opening of schools) and late Spring

24
Q

How do you treat (Rhinovirus) the common cold?

A

You don’t really. Rx = supportive care.

**Zinc might alleviate common cold symptoms (specifically those caused by rhinovirus because Zinc is a competitive inhibitor of I-CAM1)**

25
Q

A 2 year old child, who began attending day care shortly after the New Year holiday, comes home with a runny nose but is otherwise active and well. Two days later, in the middle of the night, the child wakes up with a sharp “barking” cough, fever, and is very irritable.

What is the syndrome and the virus that causes it?

A

Acute Laryngotracheobronchilitis (Croup) caused by Parainfluenza spp

**note that the infection has moved lower down the respiratory tract from larynx to main bronchi region**

26
Q

Describe the pathogenesis of parainfluenza (i.e. how do we get from nasopharyngeal mucosa to “barking” cough)

A

Start with infection in nasopharyngeal mucosa then spreads to larynx, trachea, bronchi

The cough comes when we get to the trachea: inflammation and narrowing of subglottic region of trachea (which contributes to the “bark” in the cough)

**can present with croup + stridor, hoarseness and fever**

27
Q

How do you Dx croup?

At what point in the year does parainfluenza infection peak?

A

Seasonality: mainly winter time and is gone by summer

Dx: need to see steeple sign on neck x-ray (aka tracheal narrowing)

others:

nasal wash for viral culture, immunofluorescence, PCR

serological test, IgG and IgM

28
Q

How do you treat Croup?

A

You don’t. Rx is mainly supportive care and consider steroids/nebulized epinephrine for short term relief of tracheal narrowing

29
Q

A 2 month old infant, born in October, experiences worsening fevers, cough with profuse nasal secretions, and some mild wheezes. After a week the infant has worsening symptoms and is hospitalized because oxygenation is worse.

What is the syndrome and which virus causes it?

A

Syndrome: Bronchiolitis caused by Respiratory Syncytitial Virus (RSV)

**note that this infection is lower down in the airways**

30
Q

Describe the pathogenesis of RSV

A

Nasopharynx >> small bronchiolar epithelium (type 1 + 2 pneumocytes) >> necrosis + inflammation leading to small airway obstruction (explains wheezing and respiratory failure)

31
Q

How does bronchiolitis present? (again, think about where the virus is causing disease)

A

Wheezing, increased respiratory effort (right b/c we said there’s small airway obstruction and such so breathing is going to be difficult), apnea

+ fever (somewhat low grade) preceded by URI symptoms (rhinitis, cough, congestion)

**note that this peaks in the winter time, tends to occur in young children and the symptoms basically start like URI but they keep going on**

32
Q

What are the risk factors for RSV infection?

A

RSV risk factors:

Premie babies born during winter time

Babies born with congenital heart or lung disease

**note that a long term complication of RSV is asthma or atopic disease**

33
Q

How do you Dx Bronchiolitis?

A

Clinical presentation

Labs: nasal wash for viral culture (syncytium formation), immunofluorescence, rapid antigen testing, PCR

Imaging: chest xray

Pulse ox

34
Q

What is the Rx for bronchiolitis?

A

Supportive care - respiratory support

Bronchodilators + Corticosteroids, (little benefit for infants)

(there’s also immuneprophylaxis - palivizumAb)

35
Q

An older adult nursing home patient has sudden onset of fever, chills, headache, cough, sore throat, myalgia, and malaise. For the next week he eats very little and sleeps most of the day.

What is the syndrome and which virus causes it?

A

Grippe aka influenza-like illness (don’t know about virus, probably Influenza)

**know that this is a more systemic infection (hint from malaise, fever etc)

36
Q

Describe the presentation of influenza virus

A

Abrupt Fever, severe headache (retro-orbital), severe myalgia, severe malaise (severe prostration)

    • Resp symptoms (cough, sore throat, etc.)
  • ± GI symptoms (N/V, diarrhea)
37
Q

Describe the treatments for influenza and where in the viral replication cycle the drugs work

What tools are used to Dx flu?

A

See image below**

Flu Dx: for the most part, molecular diagnostics

Rapid Ag test

Nucleic acid detection test

RT-PCR Detection test