Respiratory Viral Diseases 1 PDF

D Dr Megan Dr Lloyd  Learning Objectives To understand and be able to explain the viral diseases described here; the mechanisms of disease and the public health impact of these respiratory infections: Rhinovirus Respiratory syncytial virus Human metapneumo...

D Dr Megan Dr Lloyd  Learning Objectives To understand and be able to explain the viral diseases described here; the mechanisms of disease and the public health impact of these respiratory infections: Rhinovirus Respiratory syncytial virus Human metapneumovirus Rubella virus Measles virus Mumps virus Parainfluenza virus Adenovirus JC polyomavirus  Rhinovirus Infection of upper respiratory tract, where infection is usually limited LRT infection in babies and young children is associated with severe disease Low virulence is distinct from other Enteroviruses: Human rhinoviruses are classified into 3 species: RV-A, RV-B and RV-C Use three different receptors to enter respiratory epithelial cells ICAM-1 is used by the majority of RV-A and RV-B viruses – is target for anti-viral therapeutics  Rhinovirus infection exacerbates disease in atopic individuals Immune response in allergic individuals is biased to Th2: increased synthesis of cytokines that increase expression if ICAM-1 on the surface of bronchoepithelial cells (BECs) - likely renders cells more susceptible to infection BECs in atopic asthmatics produce decreased levels of anti-viral cytokines - increases severity of HRV infection  Respiratory Syncytial Virus RSV infects respiratory tract, does not spread systemically In newborns infection may be fatal because narrow airways are blocked by virus-induced pathology Passively acquired maternal neutralizing antibodies may be protective – this protection is impaired by pre-term delivery; low birthweight; maternal HIV infection; placental malaria; maternal hypergammaglobulinaemia No long-term immunity: reinfection may occur after a natural infection  Mechanisms by which maternal hypergammaglobulinaemia may impair transplacental IgG transfer In the presence of hypergammaglobulinaemia, high levels of non-specific antibodies are produced and saturate the finite number of Fc receptors at the placental interface https://doi.org/10.1016/j.vaccine.2022.06.034  RSV proteins antagonize the host immune response High glycosylation and structural variability of surface G-protein allows escape from neutralizing antibodies Soluble G-protein, released during viral replication, binds anti-RSV antibodies and reduces amount available for RSV neutralization Soluble G-protein also inhibits induction of TLR-mediated Type I IFN production  Rubella Infection with rubella virus causes viremia, systemic infection Antibodies limit virus spread by viremia – eg. to foetus in pregnant host Infection commonly seen in neonates 50 serotypes Causes upper and lower respiratory tract infections Erythematous rash Typically infects respiratory, digestive and ocular tracts Less frequently, infection is associated with hepatitis, cystitis, colitis, meningoencephalitis Transmitted by droplets, fecal matter, fomites Close contact; poorly sanitised swimming pools At-risk population: young children, day care centres, military camps, swimming clubs  Adenovirus Virus infects mucoepithelial cells of respiratory and gastrointestinal tract, and cornea Relatively mild upper respiratory tract infections, but can cause severe bronchopneumonia in infants; croup About 5% of childhood respiratory infections Keratoconjunctivitis is highly contagious during acute phase High rates of mortality in patients with disseminated disease, who are immunocompromised – HIV, solid organ transplant Virus persists in lymphoid tissue (tonsils, adenoids, Peyer’s patches) in immunocompromised people Type I interferon and IFN-gamma are suppressed by infection Effective Human adenovirus (HAdV)-derived vectors are limited by pre-existing humoral immunity against HAdV HAdV is a ubiquitous virus with high seroprevalence rates  JC virus Acquired via respiratory route Disseminated infection that spreads to kidneys in early life Persistent and latent infection is established in other organs including lungs, brain In immunocompromised people, virus is reactivated to replicate JC virus causes PML: progressive multifocal leukoencephalopathy, killing oligodendrocytes - demyelination Summary Viral infections of the respiratory tract are very common Many respiratory viruses are ubiquitous – they circulate continuously, exposure is lifelong Many respiratory viruses infect upper and lower respiratory tract and may cause more severe disease in certain groups, including young children and people who are immunosuppressed Many respiratory viruses disseminate and become systemic infections, infect multiple organ systems to cause severe disease that may be fatal As discussed in previous lectures, viral infections of the CNS that result in meningitis and/or encephalitis are unusual effects of common infections