West Nile Virus-Induced Membrane Structures

Replication of flaviviruses (family Flaviviridae) occurs in specialized virus-induced membrane structures (IMS). The cellular composition of these IMS varies for different flaviviruses implying different organelle origins for IMS biogenesis. The role of flavivirus non-structural (NS) proteins for the alteration of IMS remains controversial. In this report, we demonstrated that West Nile virus strain New York 99 (WNVNY99) remodels the endoplasmic reticulum (ER) membrane to generate specialized IMS. Within these structures, we observed an element of the cis-Golgi, viral double-stranded RNA, and viral-envelope, NS1, NS4A and NS4B proteins using confocal immunofluorescence microscopy. Co-transfection studies indicated that NS4A and NS4B always remained co-localized in the IMS and were associated with the same membrane fractions, suggesting that these proteins function co-operatively in virus replication and may be an ideal target for antiviral drug discovery.

Kaufusi P, Kelley JF, Yanagihara R, Nerurkar VR. Induction of endoplasmic reticulum-derived replication-competent membrane structures by West Nile virus non-structural protein 4B. PLoS ONE 2014;9(1):e84040. PMCID: PMC3896337