Dengue fever and dengue hemorrhagic fever are severe febrile diseases, and are apparently caused by four directly linked virus serotypes of the genus Flavivirus, family Flaviviridae. The other name for dengue fever is breakbone fever. Pertaining to Dengue Fever, a new research claims that cutting down the sum of fat particles in cells may be an effectual technique to thwart the dengue fever virus from replicating and spreading.
The researchers have apparently been able to slow down dengue virus assembly in a Petri dish via tentative obesity drugs that reduce cells of fat droplets. The method could avert the virus from having entry to vital building blocks; a tactic that they anticipate to be helpful in battling the incapacitating and sometimes-deadly disease.
Howard Hughes Medical Institute international research scholar Andrea V. Gamarnik and her colleagues have demonstrated that the dengue virus apparently captures fat droplets within cells and utilizes those tiny fat globules to construct new infectious virus particles.
It is known that no drugs or vaccines are present to treat dengue fever. Common symptoms are high fever and headache, joint, muscle, and eye pain, and slight bleeding from the nose and gums. A more severe form of the disease, dengue hemorrhagic fever comprises of severe bleeding that may result in death. According to WHO, dengue fever infects about 50 million people globally and kills around 25,000 people per year.
Andrea V. Gamarnik, a virologist at the Leloir Institute Foundation in Buenos Aires, Argentina, mentioned, “Dengue virus is considered the most important viral disease transmitted by mosquitoes, because of the number of cases.”
Two years ago, Gamarnik and her colleagues apparently found how the dengue virus duplicates its genetic code, which is made of RNA. But to multiply further than the infected cell to the rest of the host, the virus needs to generate an outer coating known as capsid. This outer coating is supposedly composed of several interlocking pieces called capsid proteins, which apparently surround and shield the viral RNA.
In the new researches, Gamarnik and her colleagues utilized fluorescent labels to light up the capsid proteins and observed as the virus infected human and mosquito cells. As the virus started to duplicate, it generated numerous copies of the capsid proteins. The researchers observed that these proteins amassed in rings within the cytoplasm of the cells. Additional examination illustrated that the capsid proteins were hanging on to lipid droplets, fat-filled sacs that may play a major function in lipid metabolism. In recent years, other researchers have discovered that lipid droplets apparently exert a pull on hepatitis C virus and other pathogens.
The scientists then set about indicating which segment of the dengue virus capsid attached onto the lipid droplets by methodically modifying the series of amino acids that include the capsid protein. That apparently resulted to a minute division in the middle of the molecule that is imperative for latching onto the lipid droplets. When the scientists changed this piece of the capsid, the capsid proteins no longer bundled around the lipid droplets. As a result of this variation, the rate of replication of the dengue virus supposedly dropped.
Gamarnik stated, “When we changed the capsid protein, it did not go to the lipid droplets and the cell produced no viral particles. So we concluded that the virus needs lipid droplets to replicate and form new particles.”
The experiments proposes that lipid droplets might be vital for viral replication, so Gamarnik reasoned that reducing cells of the tiny fatty orbs could hold back viral activity. Present experimental anti-obesity drugs function by dropping the amount of lipid droplets that cells generate. When a few of these drugs known as fatty acid synthase inhibitors were scattered on cell cultures, lipid droplets apparently dehydrated and manufacture of viral particles plummeted 100-fold.
Gamarnik anticipates that this prospective treatment strategy proves advantageous in the battle against the dengue virus in addition to several of its close cousins in the flavivirus family. Her team is now attempting to dissect the exact affiliation between dengue virus capsid protein and the lipid droplets, hoping to discover other weak links in the viral life cycle.
This research was published in the journal PLos Pathogens.