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Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection.
BMC Infect Dis. 2005 Aug 18; 5:64.BI

Abstract

Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV) replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-alpha, which has also been detected in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities.

METHODS

The expression of DENV antigens and inducible nitric oxide synthase (iNOS) in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis.

RESULTS

INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days), significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells.

CONCLUSION

This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production.

Authors+Show Affiliations

Departmento de Virologia, Instituto Oswaldo Cruz Fundação Oswaldo Cruz, CEP 21040-360, Rio de Janeiro, RJ, Brazil. patneves@ioc.fiocruz.brNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16109165

Citation

Neves-Souza, Patrícia C F., et al. "Inducible Nitric Oxide Synthase (iNOS) Expression in Monocytes During Acute Dengue Fever in Patients and During in Vitro Infection." BMC Infectious Diseases, vol. 5, 2005, p. 64.
Neves-Souza PC, Azeredo EL, Zagne SM, et al. Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection. BMC Infect Dis. 2005;5:64.
Neves-Souza, P. C., Azeredo, E. L., Zagne, S. M., Valls-de-Souza, R., Reis, S. R., Cerqueira, D. I., Nogueira, R. M., & Kubelka, C. F. (2005). Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection. BMC Infectious Diseases, 5, 64.
Neves-Souza PC, et al. Inducible Nitric Oxide Synthase (iNOS) Expression in Monocytes During Acute Dengue Fever in Patients and During in Vitro Infection. BMC Infect Dis. 2005 Aug 18;5:64. PubMed PMID: 16109165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inducible nitric oxide synthase (iNOS) expression in monocytes during acute Dengue Fever in patients and during in vitro infection. AU - Neves-Souza,Patrícia C F, AU - Azeredo,Elzinandes L, AU - Zagne,Sonia M O, AU - Valls-de-Souza,Rogério, AU - Reis,Sonia R N I, AU - Cerqueira,Denise I S, AU - Nogueira,Rita M R, AU - Kubelka,Claire F, Y1 - 2005/08/18/ PY - 2004/10/03/received PY - 2005/08/18/accepted PY - 2005/8/20/pubmed PY - 2006/5/6/medline PY - 2005/8/20/entrez SP - 64 EP - 64 JF - BMC infectious diseases JO - BMC Infect Dis VL - 5 N2 - UNLABELLED: Mononuclear phagocytes are considered to be main targets for Dengue Virus (DENV) replication. These cells are activated after infection, producing proinflammatory mediators, including tumour-necrosis factor-alpha, which has also been detected in vivo. Nitric oxide (NO), usually produced by activated mononuclear phagocytes, has antimicrobial and antiviral activities. METHODS: The expression of DENV antigens and inducible nitric oxide synthase (iNOS) in human blood isolated monocytes were analysed by flow cytometry using cells either from patients with acute Dengue Fever or after DENV-1 in vitro infection. DENV-1 susceptibility to iNOS inhibition and NO production was investigated using NG-methyl L-Arginine (NGMLA) as an iNOS inhibitor, which was added to DENV-1 infected human monocytes, and sodium nitroprussiate (SNP), a NO donor, added to infected C6/36 mosquito cell clone. Viral antigens after treatments were detected by flow cytometry analysis. RESULTS: INOS expression in activated monocytes was observed in 10 out of 21 patients with Dengue Fever and was absent in cells from ten healthy individuals. DENV antigens detected in 25 out of 35 patients, were observed early during in vitro infection (3 days), significantly diminished with time, indicating that virus replicated, however monocytes controlled the infection. On the other hand, the iNOS expression was detected at increasing frequency in in vitro infected monocytes from three to six days, exhibiting an inverse relationship to DENV antigen expression. We demonstrated that the detection of the DENV-1 antigen was enhanced during monocyte treatment with NGMLA. In the mosquito cell line C6/36, virus detection was significantly reduced in the presence of SNP, when compared to that of untreated cells. CONCLUSION: This study is the first to reveal the activation of DENV infected monocytes based on induction of iNOS both in vivo and in vitro, as well as the susceptibility of DENV-1 to a NO production. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/16109165/Inducible_nitric_oxide_synthase__iNOS__expression_in_monocytes_during_acute_Dengue_Fever_in_patients_and_during_in_vitro_infection_ DB - PRIME DP - Unbound Medicine ER -