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Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement.
J Infect Dis. 2006 Apr 15; 193(8):1078-88.JI

Abstract

BACKGROUND

Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown.

METHODS

The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed.

RESULTS

Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS.

CONCLUSIONS

Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS.

Authors+Show Affiliations

Medical Molecular Biology Unit, Siriraj Hospital, Mahidol University, Bangkok, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16544248

Citation

Avirutnan, Panisadee, et al. "Vascular Leakage in Severe Dengue Virus Infections: a Potential Role for the Nonstructural Viral Protein NS1 and Complement." The Journal of Infectious Diseases, vol. 193, no. 8, 2006, pp. 1078-88.
Avirutnan P, Punyadee N, Noisakran S, et al. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. J Infect Dis. 2006;193(8):1078-88.
Avirutnan, P., Punyadee, N., Noisakran, S., Komoltri, C., Thiemmeca, S., Auethavornanan, K., Jairungsri, A., Kanlaya, R., Tangthawornchaikul, N., Puttikhunt, C., Pattanakitsakul, S. N., Yenchitsomanus, P. T., Mongkolsapaya, J., Kasinrerk, W., Sittisombut, N., Husmann, M., Blettner, M., Vasanawathana, S., Bhakdi, S., & Malasit, P. (2006). Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. The Journal of Infectious Diseases, 193(8), 1078-88.
Avirutnan P, et al. Vascular Leakage in Severe Dengue Virus Infections: a Potential Role for the Nonstructural Viral Protein NS1 and Complement. J Infect Dis. 2006 Apr 15;193(8):1078-88. PubMed PMID: 16544248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. AU - Avirutnan,Panisadee, AU - Punyadee,Nuntaya, AU - Noisakran,Sansanee, AU - Komoltri,Chulaluk, AU - Thiemmeca,Somchai, AU - Auethavornanan,Kusuma, AU - Jairungsri,Aroonroong, AU - Kanlaya,Rattiyaporn, AU - Tangthawornchaikul,Nattaya, AU - Puttikhunt,Chunya, AU - Pattanakitsakul,Sa-Nga, AU - Yenchitsomanus,Pa-Thai, AU - Mongkolsapaya,Juthathip, AU - Kasinrerk,Watchara, AU - Sittisombut,Nopporn, AU - Husmann,Matthias, AU - Blettner,Maria, AU - Vasanawathana,Sirijitt, AU - Bhakdi,Sucharit, AU - Malasit,Prida, Y1 - 2006/03/09/ PY - 2005/06/30/received PY - 2005/10/28/accepted PY - 2006/3/18/pubmed PY - 2006/8/30/medline PY - 2006/3/18/entrez SP - 1078 EP - 88 JF - The Journal of infectious diseases JO - J Infect Dis VL - 193 IS - 8 N2 - BACKGROUND: Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown. METHODS: The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed. RESULTS: Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS. CONCLUSIONS: Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/16544248/Vascular_leakage_in_severe_dengue_virus_infections:_a_potential_role_for_the_nonstructural_viral_protein_NS1_and_complement_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/500949 DB - PRIME DP - Unbound Medicine ER -