Viral Respiratory Infections - RNA Viruses Flashcards
What family are the influenzaviruses in, and what are its physical characteristics?
Orthomyxovirus
Enveloped, negative-sense RNA geneome with 8 segments
What influenza protein is primarily involved in attachment and what does it bind?
Hemagglutinin (HA) - binds sialic acid (blocked via mucins)
How is influenza virus uptaken and envelope fused?
Uptaken by receptor-mediated endocytosis, endosome fuses with viral membrane due to pH drop triggering conformational change in HA
What is the function of the M2 protein?
Ion channel which allows protons to enter the virion interior, facilitating pH drop. This frees the ribonuclear complex (RNP) which is RNA + protein
This was targeted by some anti-influenza drugs, but now resistant
Where does influenza-virus replicate?
In the nucleus -> a rarity for RNA viruses
Similar to how poxviruses are DNA and replicate in cytoplasm
What is the function of transcribing RNPs?
Yields + sense RNA, which can be used to transcribe more RNA or viral genomes
What is the function of M1 protein?
Interacts with nascent RNP’s to acquire envelopes by budding thru plasma membrane
What is the function of viral neuraminidase (NA)?
Removes sialic acid from cell surface as well as surrounding mucous decoy receptors. Guarantees the virus will not re-infect a previously infected cell, and thins mucuous
What are the two protein components of HA?
Formed from HA0,
HA1 - Binds sialic acid
HA2 - Contains transmembrane domain and fusion peptide for endosome
How do Oseltamivir and Zamanivir work?
Neuraminidase inhibitors
What are the three most common influenza forms and what is the best protective antibody?
H1N1, H2N2, H3N2
Best protective antibody is anti-hemagglutinin
What is antigenic shift vs antigenic drift?
Shift - large change via genetic reassortment and coinfection of two influenza A viruses - cause pandemics
Drift - minor antigenic changes via point mutations - seasonal flu - cause epidemics
What does a typical season flu vaccine formulation contain in it?
Trivalent
Most likely H1N1 strain (Influenza A)
Most likely H3N2 strain (Influenza A)
Most likely Influenza B
What makes an influenza strain especially virulent?
When it has a broad cell tropism (not trypsin dependent, which is only in lungs), which can cause disease in young adults.
Also causes cytokine storm causing inflammation, and predisposes to nasty bacterial superinfections.
Why is trypsin required for influenza?
It is a part of human cells -> required for cleavage of HA0 into HA1 and HA2
How do influenza viruses suppression antiviral interferon responses?
Via NS1 protein, which blocks interferon-induced RNaseL pathway
What type of viruses are Paramyxoviruses?
negative (-) sense RNA genomes, unsegmented
What are the major viruses of the paramyxovirus subfamily?
Human parainfluenza viruses (HPIV 1-4), Mumps Virus, Measles Virus
(Rubella is a Togavirus)
What are the major viruses of the pneumovirus subfamily? This is a part of the paramyxoviridae family
Respiratory syncytial virus (RSV) Human Metapneumovirus (MPV)
How common are paramyxovirus infections and how are they spread?
Extremely common, especially in childhood. Spread via direct contact with respiratory secretions, aerosols, and fomites.
Most people will have had HPIV and RSV by age 2.
Are repeated infections of paramyxovirus common?
Yes, they are RNA viruses
What is croup? What clinical finding is associated with it?
Laryngotracheobronchitis - An infection and inflammation of the larynx, trachea, and bronchi, narrowing the airway leading to difficulty breathing (upper airway inflammation)
Associated with “stridor” - characteristic sound on inhalation
What viruses tend to cause croup? Do patients need treatment?
HPIV-1 is the most common cause
Other HPIV’s and RSV / MPV can cause it too.
Patient needs rapid medical attention due to respiratory distress
What do the paramyxoviruses typically cause in adults?
Laryngitis and pneumonia