Surfactant Proteins A and D: Trimerized Innate Immunity Proteins with an Affinity for Viral Fusion Proteins

J Innate Immun. 2019;11(1):13-28. doi: 10.1159/000492974. Epub 2018 Oct 5.


Innate recognition of viruses is an essential part of the immune response to viral pathogens. This is integral to the maintenance of healthy lungs, which are free from infection and efficient at gaseous exchange. An important component of innate immunity for identifying viruses is the family of C-type collagen-containing lectins, also known as collectins. These secreted, soluble proteins are pattern recognition receptors (PRRs) which recognise pathogen-associated molecular patterns (PAMPs), including viral glycoproteins. These innate immune proteins are composed of trimerized units which oligomerise into higher-order structures and facilitate the clearance of viral pathogens through multiple mechanisms. Similarly, many viral surface proteins form trimeric configurations, despite not showing primary protein sequence similarities across the virus classes and families to which they belong. In this review, we discuss the role of the lung collectins, i.e., surfactant proteins A and D (SP-A and SP-D) in viral recognition. We focus particularly on the structural similarity and complementarity of these trimeric collectins with the trimeric viral fusion proteins with which, we hypothesise, they have elegantly co-evolved. Recombinant versions of these innate immune proteins may have therapeutic potential in a range of infectious and inflammatory lung diseases including anti-viral therapeutics.

Keywords: Collectins; Fusion proteins; Innate immunity; Structure; Surfactant proteins; Trimeric proteins; Virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Collectins* / chemistry
  • Collectins* / immunology
  • Humans
  • Immunity, Innate*
  • Lung / immunology
  • Lung Diseases / immunology
  • Lung Diseases / therapy
  • Lung Diseases / virology
  • Protein Multimerization
  • Pulmonary Surfactant-Associated Protein A* / chemistry
  • Pulmonary Surfactant-Associated Protein A* / immunology
  • Pulmonary Surfactant-Associated Protein D* / chemistry
  • Pulmonary Surfactant-Associated Protein D* / immunology
  • Receptors, Pattern Recognition* / chemistry
  • Receptors, Pattern Recognition* / immunology
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / immunology*
  • Viruses / immunology


  • Collectins
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Receptors, Pattern Recognition
  • Viral Fusion Proteins