[Frontiers in Bioscience S2, 527-546, January 1, 2010]

Role of surfactant protein A and D (SP-A and SP-D) in human antiviral host defense

Kevan L. Hartshorn

Boston University School of Medicine, Department of Medicine, Boston MA

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. SP-A and SP-D in human antiviral host defense
3.1. Preliminary anatomic considerations
3.2. Clinical and epidemiological evidence for a role of SP-A and SP-D in respiratory viral infection
3.2.1. Genetic epidemiology
3.2.2. Acquired deficiencies of SP-A or SP-D
3.3. Important biochemical and structural points for understanding functional attributes of SP-A and SP-D
3.4. Detailed survey of antiviral activities and mechanisms of inhibition
3.4.1. IAV
3.4.1.1. Evidence that collectins inhibit IAV and mechanism of inhibition
3.4.1.2. Structural requirements for IAV inhibition by SP-D
3.4.1.3. The role and mechanism of SP-A in inhibition of IAV
3.4.1.4. The unique properties of porcine SP-D
3.4.1.5. The potential role of MBL in IAV infection
3.4.2. RSV
3.4.3. Parainfluenza virus
3.4.4. Adenovirus
3.4.5. SARS
3.4.6. Ebola
3.4.7. Herpesviruses
3.4.8. HIV
3.5. Modulation of innate and adaptive immune responses to viral infection
3.5.1. Innate immunity
3.5.1.1. Gp340
3.5.1.2. Complement
3.5.1.3. Defensins
3.5.1.4. Phagocytes
3.5.1.5. Toll like receptors
3.5.2. Adaptive immunity
3.6. Role of SP-A or SP-D in bacterial super-infection
3.7. Important areas for future research
3.8. Therapeutic implications
3.8.1. Recombinant SP-D as therapy
3.8.2. Up-regulation of surfactant collectin expression
4. Summary and perspective
5. Acknowledgements
6. References

1. ABSTRACT

SP-A and SP-D contribute to host defense against respiratory viral infection. The most extensive body of evidence relates to influenza A viruses (IAV), and evidence from gene-deleted mice also indicate a role for surfactant collectins in defense against respiratory syncytial virus (RSV) and adenovirus. Some important respiratory pathogens including rhinovirus and metapneumovirus have not yet been examined. Viral pathogens that enter the body via the respiratory tract (e.g., Ebola virus), replicate in the lung (e.g., human immunodeficiency virus or HIV) or infect the lung in immuno-compromised hosts (e.g., herpes simplex virus or HSV) are inhibited by collectins. SP-A and SP-D are expressed in other mucosal surfaces (e.g., the eye or genitourinary tract) where they may play roles in antiviral defense. In addition to direct antiviral activities, the SP-A and SP-D modulate innate and adaptive immunity and inflammation associated with infection. The relative importance of antiviral vs anti-inflammatory effects of SP-A and SP-D in viral infections and the potential use of these collectins as therapeutics for viral infections are under investigation.