Viral Respiratory Pathogens

Respiratory viruses are the most common cause of human infection worldwide. Most possess RNA genomes; because RNA-dependent RNA polymerases lack proofreading capability, RNA viruses mutate rapidly, generating new antigenic variants that evade host immunity. This poses a major challenge to vaccine and antiviral development.

Influenza A is the most important respiratory virus globally. It is an enveloped RNA virus (orthomyxovirus) with a segmented genome encoding two key surface glycoproteins: haemagglutinin (HA) and neuraminidase (NA). HA mediates attachment to sialic acid on respiratory epithelial cells; NA cleaves sialic acid to release daughter virions. Antigenic drift (accumulated mutations in HA/NA genes) causes seasonal variation. Antigenic shift (genetic reassortment between human and animal influenza A strains via co-infection of an intermediate host) produces novel pandemic strains to which the population has no pre-existing immunity.

Respiratory syncytial virus (RSV) is a paramyxovirus and the leading cause of bronchiolitis and pneumonia in infants under 12 months. RSV infection in early childhood increases the risk of subsequent wheezing and asthma, and it is a major cause of otitis media.

Rhinoviruses (picornaviruses) cause the majority of common colds. They replicate optimally at 33 degrees Celsius (nasal cavity temperature) and infect via the ICAM-1 receptor. With over 100 serotypes, naturally acquired immunity is highly strain-specific, making vaccine development challenging.

Adenoviruses are unusual among respiratory viruses in possessing a double-stranded DNA genome, making them more genomically stable than RNA viruses. They cause pharyngitis, conjunctivitis, and pneumonia. Coronaviruses (including SARS-CoV-2) are large enveloped RNA viruses whose spike protein binds ACE2 on respiratory epithelial cells. SARS-CoV-2 undergoes both antigenic drift and receptor-binding domain mutations, reducing the efficacy of neutralising antibodies over time.