Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec;33(12):13866-13881.
doi: 10.1096/fj.201901095RR. Epub 2019 Oct 22.

Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro

Takao Sanaki  1   2 , Masato Wakabayashi  3 , Takeshi Yoshioka  3 , Ryu Yoshida  1 , Takao Shishido  1 , William W Hall  4   5   6 , Hirofumi Sawa  4   7   5 , Akihiko Sato  1   2
Affiliations

Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro

Takao Sanaki et al. FASEB J. 2019 Dec.

Abstract

Dengue fever is an acute febrile infectious disease caused by dengue virus (DENV). Despite the significant public health concerns posed by DENV, there are currently no effective anti-DENV therapeutic agents. To develop such drugs, a better understanding of the detailed mechanisms of DENV infection is needed. Both lipid metabolism and lipid synthesis are activated in DENV-infected cells, so we used lipid screening to identify potential antiviral lipid molecules. We identified 1-stearoyl-2-arachidonoyl-phosphatidylinositol (SAPI), which is the most abundant endogenous phosphatidylinositol (PI) molecular species, as an anti-DENV lipid molecule. SAPI suppressed the cytopathic effects induced by DENV2 infection as well as the replication of all DENV serotypes without inhibiting the entry of DENV2 into host cells. However, no other PI molecular species or PI metabolites, including lysophosphatidylinositols and phosphoinositides, displayed anti-DENV2 activity. Furthermore, SAPI suppressed the production of DENV2 infection-induced cytokines and chemokines, including C-C motif chemokine ligand (CCL)5, CCL20, C-X-C chemokine ligand 8, IL-6, and IFN-β. SAPI also suppressed the TNF-α production induced by LPS stimulation in macrophage cells differentiated from THP-1 cells. Our results demonstrated that SAPI is an endogenous inhibitor of DENV and modulated inflammatory responses in DENV2-infected cells, at least in part via TLR 4.-Sanaki, T., Wakabayashi, M., Yoshioka, T., Yoshida, R., Shishido, T., Hall, W. W., Sawa, H., Sato, A. Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro.

Keywords: Toll-like receptor 4; inflammatory responses; lipid screening.

PubMed Disclaimer

References

REFERENCES

    1. Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O., Myers, M. F., George, D. B., Jaenisch, T., Wint, G. R., Simmons, C. P., Scott, T. W., Farrar, J. J., and Hay, S. I. (2013) The global distribution and burden of dengue. Nature 496, 504-507
    1. Brady, O. J., Gething, P. W., Bhatt, S., Messina, J. P., Brownstein, J. S., Hoen, A. G., Moyes, C. L., Farlow, A. W., Scott, T. W., and Hay, S. I. (2012) Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl. Trop. Dis. 6, e1760
    1. Srikiatkhachorn, A., Krautrachue, A., Ratanaprakarn, W., Wongtapradit, L., Nithipanya, N., Kalayanarooj, S., Nisalak, A., Thomas, S. J., Gibbons, R. V., Mammen, M. P., Jr., Libraty, D. H., Ennis, F. A., Rothman, A L, and Green, S. (2007) Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographic study. Pediatr. Infect. Dis. J. 26, 283-290; discussion 291-292
    1. Rigau-Pérez, J. G., Clark, G. G., Gubler, D. J., Reiter, P., Sanders, E. J., and Vorndam, A. V. (1998) Dengue and dengue haemorrhagic fever. Lancet 352, 971-977
    1. Pan American Health Organization. (2016) Dengue: guidelines for patient care in the region of the Americas. Pan American Health Organization, Washington, DC

Publication types

MeSH terms

LinkOut - more resources