RSV, MPV Flashcards
Paramyxoviridae classification
Subfamily- Paramyxovirinae : respivirus (PArainfl 1 and 3), rubulavirus (Parainf 2,4, mumps), morbilivirus (measles), henipa (nipah, hendra)
Subfamily- Pneumovirinae: Pneumovirus- RSV, metapneumovirus - MPV
Homology between RSV and MPV; homology between genotypes of MPV
40%
80-90%; max varaition with G and SH
Genome of MPV vs RSV
MPV: F, G, SH, M, M2-1- transcription elongation factor, M2-2 RNA synthesiss regulatory factor, NP, P, L
RSV: extra NS
MPV- fusion and attachment by; receptor
The heptad repeat domain A in the F protein appears to be critical for fusogenecity,
G protein helps tether virus particles to the cell surface and confers optimal infectivity but is not critical for viral attachment.
Type 2 alveolar and bronchiolar epithelial - proteo- glycan, integrin, and C-type lectin receptors
Genotypes of MPV
two major geno- types (A and B) and five subgroups with two sublineages (A1, A2a, A2b, B1, and B2). - based on F and G
MPV vs RSV
1) hMPV lacks two nonstructural proteins found in RSV that are known to inhibit host interferon production, and likely uses other mechanisms to subvert innate immune responses.32,33 In human volunteers, peripheral blood mononuclear cells stimulated with hMPV produce a stronger innate and weaker adaptive cytokine response than RSV.
2) pre and postfusion F- same neutralising epitopes
3)omewhat older than for RSV infection, with highest rates noted between 6 and 11 months of age
4) febrile seizures, ataxia, and encephalitis appear to be approximately 10 times more common in children with hMPV compared to those infected with RSV.92
5) fever more common
6) generally peaking
1 to 2 months later than RSV.
MPV- ab against (immunogenic); neutralising ones
F>G, SH; F
Reinfection in RSV and MPV is possible because
reinfections
occur throughout life in part due to poor development of T- and B-cell
immunity.
Lymphopenia and receipt of cytotoxic therapy
are risk factors for severe hMPV disease, suggesting that cellular immunity
is important for hMPV illness resolution.
MPV- age group; seropositivity; % for hospitalisation
ubiquitous pathogen that affects all age groups. Seroprevalence studies indicate that by age 5 years, most children
2% to 3% of all symptomatic respiratory infections among children in the first 5 years
13% of hospitalizations in children
2% of acute respiratory illnesses in the general adult population are due to hMPV.
coinfection and seasonality of MPV
winter seasonality of hMPV, coinfection with other viral and bacterial respiratory pathogens ranges from 5% to 60%
Streptococcus pneumoniae,
The presence of the neuraminidases of influenza virus appears to promote the adherence of bacteria to the respiratory epithelium, whereas replication of hMPV is required to increase superinfection of pneumococcus in the respiratory tract.58 In addition, hMPV infection appears to impair neutrophil recruitment to the airways,
leading to delayed bacterial clearance.
MPV- seasonality
temperate climates, the virus circulates
predominantly in the late winter and spring months, - Low temperature and
vapor pressure and increased wind speed a
MPV- clinical features
mild upper respiratory infection to bronchiolitis and severe pneumonia
most infections are symptomatic.
incubation period of about 5 to 6 days
Most young children with hMPV infection exhibit fever, cough, sore throat, and rhinorrhea
seizures, ataxia, and encephalitis
pharyngitis, conjunctivitis, maculopapular rash - less common
bronchiolitis (47%–84%), asthma (common in childdren younger than 3 yrs- older rhinovirus) (11%–25%), and pneumonia (11%–17%); croup
perihilar infiltrates (87%), hyperinflation (69%), patchy opacities, and atelectasis
risk factors: emale sex, prematurity, esophageal reflux, underlying heart and lung disease, lack of breastfeeding, vitamin D deficiency, and household crowding.
Adult: Healthy adults generally present with mild influenza-like illness and common cold syndromes, with some remaining asymptomatic.36,50,115 In addition to respiratory illnesses, a mononucleosis-like syndrome due to hMPV ; COPD, asthma worsening
Diagnosis of MPV
RT-PCR: conserved regions of the F and N genes; sputum, BAL> Nasal washes and nasopharyngeal swabs; PCR may occur for up to 4 weeks in children with primary infection,
IFA: less sensitive than RT-PCR, (low load)
Serology: against F; fourfold rise in antibody titer or seroconver- sion, and thus clinical utility is limited.
Viral culture: rhesus monkey kidney (LLC-MK2) cells in medium containing trypsin. small, round, granular, and refringent cells without large syncytia,
Treatment of MPV
supportive
careful of glucocorticoids - antiinflammatory benefits may be offset by the blunting of immune responses that control viral replication.
enhanced hMPV replication in human primary bronchial epithelial cells and reduced viral apoptosis. The effect was suppressed by the use of adjuvant recombinant interferon therapy, raising potential therapeutic strategies.
Ribavarin, favipravir, DAS181 - in studies
Spread of MPV
direct contact with infected secretions through fomites or large-particle aerosols (droplet)
RSV: aka, hosts
chimpanzee coryza agent (CCA). humans and chimpanzee
RSV: ab against; neutralisation; binding by whom; receptor; cells
G and F; prefusion F has more epitopes
G and F; G- CX3C, F- nucleolin in resp epi cell
resp epi cells - cilliated columnar, type I and II pneumocytes, RSV can also infect macrophages, dendritic cells, and T and B cells.
Seeasonality of rsv
RSV infections are ubiquitous
In temperate climates, outbreaks occur primarily in late fall through early spring and spread across the United States over 20 or more weeks, generally from October to May. In warmer climates, RSV activity may be more prolonged or even present throughout the year.
Genotypes of RSV and homology
2- a and b
81% - most diversity in G protein
CF of RSV - infants; types and course
rarely asymptomatic
40% to 90% of bronchiolitis (both expiratory and inspiratory obstruction may be evident, rapid variability in the presence and intensity of physical findings, marked transient swings in oxygen saturation )
up to 50% of pneumonia admissions
tracheobronchitis cases, 10% to 30%
2% to 10% of croup
The highest hospitalization rates (25.9/1000) were in infants 1 month of age, slowly decreasing thereafter. - max before 6 months - all before 5 years
However, severe disease rarely occurs after primary infection in healthy children.
RSV usually starts with upper respiratory tract illness with nasal congestion and cough. Low-grade fever lasting 2 to 4 days occurs in most infants early in the illness. fever is frequently absent by the time of lower respiratory tract involvement. cough may become more prominent and productive, followed by increased respiratory rate, dyspnea, and retractions of intercostal muscles.
RSV: IP and viral shedding
an incuba- tion period of 2 to 5 days.
Shedding duration is typically 7 to 10 days, but virus can occasionally be detected for 30 days.85 Increased viral load has been associated with greater disease severity.
Main pathogenesis of RSV causing bronchiolitis - why infants more?
characteristic proliferation and necrosis of the epi- thelium of the bronchioles develop. Small airways become obstructed from sloughed epithelium and increased mucus secretion. partial obstruction - hyperinflation, complete obstruction - atelectasis
1) smaller airway- more resistance
2) young infants are at increased risk for developing atelectasis because collateral channels that maintain alveolar expansion in the presence of airway obstruction are not yet well developed.
3) Despite a relatively short half-life of 28 to 40 days, maternally derived antibodies have been correlated with protection in some, but not all, studies.
4)neutralizing antibody responses are blunted in infants younger than 6 months of age owing to a dampening effect of maternal antibody.
5) Infants infected in the first several months of life have higher levels of Th2-type cytokines in nasal secretions than older infants - IL-4 and IL-13 also augment isotype switching to IgE, and a Th2-biased response has been correlated with wheezing, more severe disease, and greater cellular inflammation and eosinophilia in the lung.
rationale for maternal vaccination in rsv
26% reduction in hospitalization during the first 6 months of life for every twofold increase in cord blood neutralizing antibody.115 In addition, a study found that higher levels of antibody to prefusion-F and G proteins of RSV and neutralizing antibody were associated with less severe disease in the first few months of life.
Serological diagnosis of RSV
IgM) antibody appears within several days but is transient and detectable usually only for a few weeks.95 IgG antibody appears during the second week, peaks in the fourth week, and begins to decline after 1 to 2 months.
against F
Adult: Following natural infection, 75% of adults demonstrate a fourfold or greater decrease in titer, returning to preinfec- tion titers within 2 years in most cases.
