#10 Respiratory viruses Flashcards
Transmission of respiratory viruses
Transmission→ Replication in URT→ Upper ans sometimes lower infections and diseases
Picornavirdae virus family:
genome:
env:
diseases
+RNA,
non enveloped
Rhinovirus, Coxsackie virus, echovirus, enterovirus
Coronavirdae
genome
enveloped
diseases
+RNA
eneveloped
-Coronavirus, SARS-CoV, MERS-CoV
Coronavirus, SARS-CoV, MERS-CoV examples of
Coronavirdae
+ RNA, enveloped
Rhinovirus, Coxsackie virus, echovirus, enterovirus examples of
Picornavirdae
Orthomyxovirdiae
genome
enveloped
viruses
-RNA
env
Influenza A, B, C virus
Influenza A, B, C virus are what family
orthomyxovirdae
-RNA env
Parmyxovirdae
genome
envelope
viruses
-RNA
env
Parainfluenza, respiratory syncytial, metapneumovirus, Hendra and Nipavirus, measles virus
Parainfluenza, respiratory syncytial, metapneumovirus, Hendra and Nipavirus, measles virus
all Parmyxovirdae virsuse
-RNA, env
INfluenza A, B and C family of viruses
Orthomyxovius
Genus of influenza A, B and C
(Thogotovirus)
Typing of influenza A, B C
Based on matrix and nuceloprotein antigens
Subtyping of influenza based on
Based on Hemagluttin and Neuramidase
H1N1 or H2N2
Influenza stucture:
envelope virus with matrix proteins that adds structure
: key for attachement and fusion to cellular membrane
Hemagluttinin
key for release of protein virions
Neuramidase:
Ribonuclear protein of influenza has____ individual segments of RNA. Complexed with proteins key in polymerase activity
8
Genome of influenza and affect on what it brings with it to host cells
- RNA
- there is a (-) sense RNA thus virus has to carry a polymerase with it to begin replication
Drift: minor change in either
HA or NA or both
Drift: HA mutations are primarily found in the ______combining sites in the HA protein
4 antibody
*Drifts cause______ We’ll see same influenza subtype (H3N2 for example) with dif strains
EPIDEMICS!!!
Shift: major_____ shifts.
occur infrequently either
antigenic
in HA alone or NA as well.
Cause of genetic shift
D/t gene reassortment btwn human and animal strain
Shifts cause _______
*Pandemics
example of shift causing pandemic
H1N1 vs H2N2 or in 2009 the swine flu (H1N1) see avian and human coinfect a pig which has both α2,3 and α2,6 receptors
Pathogenesis of Influenza:
- acute respiratory disease
- infects ciliated epithelial cells lining URT, trachea and bronchi
- Replication of virus responsible for destruction of respiratory epithelium
- Cell damage d/t virus activated CTL
- Viremia is NOT a mjor role in pathogenesis
Influenza causes
___________
infects ________ lining URT/trachea/bronchi
-acute respiratory disease
ciliated epithehlial cells
What is responsible for destruction of epithelium during influensa
- Replication of virus responsible for destruction of respiratory epithelium
- Cell damage d/t virus activated CTL
Role of viremia in influenza patho
Viremia is NOT a mjor role in pathogenesis
Common Pathogenesis if influenza
Aerosol inocculation of virus→ Replicates in repsiratory tract (causes antiB, Tcell response, Interferon induction)→ Desquamination of mucus→Influenza syndrome
Aerosol inocculation of virus→ Replicates in ________ (causes antiB, Tcell response, Interferon induction)→______ of mucus→Influenza syndrome
repsiratory tract
Desquamination
Influenza pathology:
Less frequent: Secondary bacterial infection
lead to pneumonai, primary viral pneumonia and CNS/mscl involvment
Host reponst to influenzaL
Antibody and T cell response:
T cell response and Interfuron induction:
provides for future protection
push for influenza syndrome
Pathogensis of influeza
Infterfeuron induction:
Patho change in respiratory:
Cell mediated:
Infterfeuron induction: 1 day
Patho change in respiratory:6 days
Cell mediated: day 4
Lab detection of influenza
Virus in respiratory secreations:
Rise in virus-antiB:
1 day
day 7
Clincal disease of influenza
Symptoms, influenza: 2 days
Incubation:
2 days before symtpoms
Acute influenza in adults
Rapid onset fever, malaise, myalgia, sore throat, nonproductive cough
Acute influenza kids
Acute disease sim to adults but higher fever, GI symptoms (pain and vomit) otitis media, myositis, more frequent croup
Complications of virus (influenza
Primary viral pneumonia, secondary bacterial pneumonia, myosistis and cardiac involvement
Neurologic syndromes: Guillain-Barre, Encephalopathy, Encephalitis, Reye Syndrome
Clincal signs/epidemiology and then Lab diagnostics for INfluenza:
- rapid antiG capture—
- rt-PCR tells us
detects nucleoprotein (NP) or both influenza A and B virus w/in 15 mins
what type we are dealing with
Overview on Replication
- Binds to sialic acid receptors–>Endocytosed and fuses with vesicle mmb and uncoated
- ->Transcription/replication of genome occurs IN THE NUCLEUS (most RNA’s do this in cytosol)
- ->Viral proteins synthesized and helical nucleocapsid segments form and assicate with M1 protein-lined membranes containing M2 and the HA and NA glycoproteins
- ->Virus buds from plasma membrane with 8-11 nucleocapsid segs
influenza will bind to ______ to get endocytosed and fuses with vesical membrane to get uncoated
sialic acid
Transcription and replication of genome for influenza occur in_____
Nucleus (most RNAs don’t do this)
Viral proteins of influenza synthesized and helical nulceuocapsid segments form and associated with:
M1 proteins lined proteoins containing M2 as well as HA and NE
When influenza virus buds, has ____ nucleocapsid segments
8-11
Key on uncoating:
The _______will activate the M2 ion channel of virus to mediate fusion to virus can release contents and break down matrix protein and HA
drop in pH
Influenza Virus Cell Receptor:
_____-_____: with NA mediating the fusion
Sialic acid—Galactose
Avain vs human linkagers
~~~ 2,3 link is more avian, while 2,6 is our URT : pig is good for co-infection bc has both receptors
vaccine info… confuses me on influenza
Formalin inactivated
attenuated infectious:
Experimental
Formalin inactivate: mix of prevalent antigenic types (both HA and NE)
Attenuated infectious viruse: intranasal admin
Experimental vaccines: DNA vaccines and revese genetics
amantadine and rimantidine—
Ribavarin-
Zanamivir and Oseltamivir are
inhibit uncoating via blocking M2 protein
inhibits synthesis of viral RNA
NE inhibitors
Cauuses common cold, over 150 serotypes
Rhinovirus
Rhinvoris is a _______virus
picornavirus
Sytptoms and cause of rhinovirus
headache, cold sore thoat, mucopurlent or runny nose
dt inflammation response: infect cells release BK and His
infected cells with rhino release
BK and HIS = symptoms
Rhion is temp sensitive, grwos best
at 33 over 37 (stays in the nose, URT)
what is key to limit reinfection with rhinovirus
IgA
Transmission of rhinovirus
respiratory secreations: ind–ind via fomites
genome and env of rhinovirus
ssRNA (+)
Icosahedral
no env
(type of Picornavirus)
Viral cycle of Rhinovirus
I-cam 1 Receptor and then bind, endocytosis, uncoat (conformational change injection structure), make single polyprotein which gets proteolytically processed, and RNA into capsid
cause common cold→ 2nd most prevalent cause representing 10-15% of total
~watery eyes, sneeze, congestion, sore throat, fever, chills, headache, cough
Coronaviruses:
Coronavirus is a
limited to:
optimal temp:
vaccine
picornavirus
URT, epitheial cells
33-35
no vaccine
SARS or Severe Acute Respiratory sydrome is a:
Coronavirus
Outcome of SARS
where do you get it
Fatality: 10% people with illness See 8500 cases worldwide, 300 in US
Source~ bats or animals sold in markets
not seens since 03
HOw do we tx/control SARS
no vaccine or anti-viral, containment is key!
First seen in 2012 and is different from SARS-CoV by genome sequencing
MERS-CoV
how is MERS-CoV (middle east respiratory) dif then SARS
diff cellular R then SARS
Origin/spread and tartget of MERS-CoV
Case originate in ME and serious cases tend to have underlying medical issues and we see that nonsocial infections documented… seen still birth documented and Currently see MERS-CoV have caused 400 cases to date→ and people IG have underlying issues
Morbillivirus (measles) Paramyxovirus (Parainfluenza and mump) Pnemovirus (RSV) Hepinavirus (Hendra and Nipah) all in what family
Paramyxoviridae
The F protein in the Paramyxovius family
Fusion protein virus entry
The HN protein in the Paramyxovirus family
H is for Hemagglutinin viurs attacthment
the N is for neuramidase or virion release
HN protein is not present in which Paramyxovirus
RSV
NS1 and NS2 proteins in Paramyxovirus do what
nostructual proteins, modulate immune response, key inviv
Paramyxovirus genenom
-ssRNA
Replication of paramyxovirus:
see attachment and fusion (antiB work against the attachment and fusion) → RNA replicaion which is in:
stays in CYTOPLASM (doesn’t travel to nucleus) and get replication of RNA and then transcription of mRNA to protein virions
Where does RNA replication occur for paramyxoviruses
CYTOPLASM
then transcription to mRNA—> to get protein virions
What is human parainfluenza virus
Common cuase of acute URT and LRT infections in infants, young, elderyly and immunocompromised
HPVI3 is simular to _____ bc its a common cause of Lower respiratory infections in first year of life and is more sersious
RSV
HPVI seen later in life then 3 yrs and are common cause of Croup
HPIV1 and 2
common cuase of LRI such as bronchitis in first yr life and more serious
Humanparainfluenza 3 or HPVI3 and RSV
HPIV strain thast asympotomatic
HPIV4
HPIV1 and 2
seen later, common cause of Croup
______(cDNAs) for the HPIVs help identify and attenuate mutations and incrementally attenuate
HPIV to use as _______
Reverse genetics
intranasal vaccines.
MOst common cause of fatal acute respiratory tract infection in infant and young
respiratory syncytial virus (RSV)
By age ___ virually everyone infected with RSV and reinfections occur:
by 2
throughout life
RSV
family
species
genome
Paramycovirdase
pneumovirus
-ssRNA
RSV causes localized infection of______ and no viremia or system spread
respiratory tract
RSV
-Pneumonia: resluts from _____spread of virus
-Bronchiolitis: most likely from:______
-
cytopathologic s
hosts immune respnose
RSV: narrow airways of young easily obstructed by
virus-induced pathologic effects
RSV:- infection
maternal antiBs
naturaul infection agains re-infection
don’t protect infant from infection
reinfection doesn’t protect from re-infection
Respiratory synctial virus-
Pathogenesis: in bronchiolitis, ariway is obstructed from swelling of bronchiole wall and see _______
multi-nucleated Giant Cells.
RSV typical giant cells are in the_____ trancytoplasmic inclusions
pink
RSV
Th1: Common in______→ see INFγ and B cell activation leading to antiG presentation, cytolysis, antiviral cytokines and viral clearance dt/ cell mediated immunity
adults
Th1 path
cell mediated immunity
Th2: often seen in ____: see IgG’s and E and IL-4 to causes _______ and IL-5 for eosinos (wheezing)
–more of a prostaglanding D2 and histamine response or move of a _____
infants
IgG/E and IL-4 to mast cell activaiton
histamine and inflammatory resposne
RSV in chilren
Febrile rhinitis and pharnygitis
children under 1 year
Bronchiolitis, pneumonia, both
Fever/cough and cyanosis
Tx or prevention of RSV
healthy
tx is supportive, Oxygen, IV fluids and nebulized cold steam
TX of RSV premies/immunocompromise
aerosolized rivavirin
Tx or RSV in prematures
Passive immunization with anti-RSV + humanized monoclonal antiB against viral fusion protein
VAccine status for RSV
No vaccine currently available: inactived have shown poor results w/ incrased disease severity upon naturla infection
Live attenuated→ no increase in disease severity w/ natural infection but poor long term productionq
looks simular to RSV and first seen in 2001
Most severe in infants, elderly or immunoC or w/ pulmonary disease and COPD
hMPV: human Metapenumovirus:
hMPV: human Metapenumovirus
genome
family
species
-ssRNA
pneumovirus of paramyxovirdae
Second most common cause of LRI in young children after RSV
Recently seen that _______ accounts for 4.5% of hospitalization for acute RTI in adults over 50 during winter
hMPV
By ___years of age all children are seropositive for hMPV
5
Tx for hMPV
have IVIG which are humanized monoclonasl specific for hMPV fusion and potein MAB 333
what do we do for serious hMPV infection
Ribivarin IV + IVIG
Hendra and Nipha viurs are
Paramyovirdae
Hendra and Nipha are dangerous because
high mortality rate–respiritary virus
from bats to people
Specturm of disease for adenovirus
Spectrum disease
Respiratory (pharyngitis)
GI or conjuctivitis
Hemorrhagic cystisis
in adenovirus ________ can lead to systemic infection –> viremia
Respiratory infection
Adenovirus: Systemic infections seen in_________ pts
immunocompromised
Respiratory can cause _________, persistant virus shedding or lymphoid infections
productive infection
*The acute respiratory disease seen in
military recruites d/t barrack style living thus get vaccine for it
Adenovirus spread:
Eye/URT → Upper respiratory→ Lower resp or GI → lymph nodes→ viremia→ to either skin or organs → latency or resolution