Navigation Links
The Dengue Virus Unplugged

The manner of transmission of mosquito-borne viruses is well known; a bite on the body that allows the virus to make an entry into the blood stream. But what happens next that causes the virus //to multiply and take hold of its victim. Researchers led by a Howard Hughes Medical Institute (HHMI) international scholar in Argentina have been able to point at a genetic element which helps the dengue virus multiply, which is the main cause of the potentially fatal illness termed as dengue hemorrhagic fever.

In the August 15, 2006, issue of the journal Genes & Development, published online August 1, 2006, virologist Andrea Gamarnik and colleagues at Leloir Institute Foundation in Buenos Aires, describe how a viral enzyme recognizes and amplifies the genetic material needed to assemble new dengue viruses. Their findings provide the first model for RNA replication in the family of viruses that includes West Nile, St. Louis encephalitis, and hepatitis C.

These viruses, known as flaviviruses, cause millions of cases of human illness each year, but no vaccines or antiviral drugs exist to control most of the infections. Dengue fever is endemic in many tropical and subtropical regions, causing a severe, flu-like illness that sickens more than 50 million people and kills 25,000 each year.

Once a virus enters a host cell, its top priority is to copy its genetic code so that it can make more virus. Flaviviruses are so efficient at this task that they can churn out tens of thousands of copies of their genome--which is composed of ribonucleic acid, or RNA--within hours of infecting a cell.

For dengue and other flaviviruses, the first step is to produce viral proteins, including an enzyme that can copy RNA. But the viral RNA is not the only RNA in an infected cell. So once the enzyme, called RNA-dependent RNA polymerase (RdRp), is produced, it finds itself surrounded by cellular RNA, creating a dilemma: How does RdRp distinguish vir al from cellular RNA, to replicate the right molecule?

Last year, Gamarnik got her first hint when her group identified two RNA sequences located at the ends of the dengue virus genome. These short sequences interact during RNA replication, shaping the viral RNA genome into a circle. Gamarnik's team published those findings in the June 2005 issue of the Journal of Virology.

Further studies of the dengue virus life cycle revealed another piece of the virus's RNA that recruits the enzyme RdRp. Found at one tip of the genome, that sequence adopts a characteristic stem-loop structure that the scientists suspected might be important to its function.

To test whether RdRp was relying on that stem-loop shape to recognize the viral RNA, the scientists created copies of the dengue genome with minor changes that would alter its structures. The mutated RNAs were then inserted into mosquito cells or hamster cells to see if the viral RNA would be copied.

To their surprise, the scientists found that the stem-loop or SLA sequence is essential for viral replication. Changes in even one or two building blocks in this structure were enough to halt the replication process. 'That told us that RdRp probably discriminates the viral RNA by recognizing SLA,'Gamarnik said.

To confirm the vital link between RdRp and SLA, the researchers allowed virus particles that couldn't replicate to evolve in cells grown in lab dishes. Spontaneous mutations that occurred in the SLA often restored RdRp's activity and full viral replication capacity.

The scientists didn't expect to find that RdRp activity relies on a sequence at the far end of the genome, thousands of nucleotides away from the end where the enzyme begins copying the RNA.

The new discovery makes sense, Gamarnik said, because the circular shape adopted by the virus brings the distant ends of its genome together. At first we were puzzled by the cyclizati on feature of this virus, said Gamarnik. 'We now recognize that it serves a role in bringing the SLA promoter near the initiation site.'

Paul Ahlquist, an HHMI investigator at the University of Wisconsin-Madison and an expert on RNA viruses, said that the Gamarnik team's findings explain prior observations from her lab and others that binding between the 5-prime and 3-prime ends of the viral genome is required for replication of dengue and several other medically important flaviviruses. "These insights suggest possible mechanisms by which flaviviruses may regulate some distinct replication steps, and might ultimately provide foundations for new antiflavivirus strategies, Ahlquist said.

Source : Eureka Alert


Related medicine news :

1. Dengue Outbreak in Kolkata, Four Dead
2. Dengue in Delhi – 26 Cases reported and 3 dea
3. Dengue fever in Delhi after the Monsoon
4. Dengue Claims 15 Lives In West Bengal
5. Dengue Epidemic in West Bengal: Over 1000 New Cases and 15 dead
6. 45 People die in West Bengal due to Dengue and suspected Japanese Encephalitis
7. Vaccine For Dengue Fever On Trial In Asia-Pacific
8. Dengue Fever Claims Five Lives In Pakistan
9. Fear Of Dengue Epidemic Looms Large: Fever Kills Five in Pakistan
10. Delhi Launches Special Drive to Check Dengue Spread
11. MCD Takes Steps To Prevent, Control Dengue
Post Your Comments:

(Date:11/27/2015)... Raleigh, NC (PRWEB) , ... November 27, 2015 , ... ... most effective ways to treat it. Surviving Mesothelioma has just posted the findings ... Researchers at University Hospital Zurich analyzed the cases of 136 mesothelioma patients who were ...
(Date:11/27/2015)... ... November 27, 2015 , ... ... 27th edition of USA Today in Atlanta, Dallas, New York, Minneapolis, South Florida, ... The digital component is distributed nationally, through a vast social media strategy and ...
(Date:11/27/2015)... Wilmington, DE (PRWEB) , ... November 27, 2015 ... ... a member of the well-respected Microsoft Dynamics SL User Group (MSDSLUG). Recognized as ... is an independent group of Microsoft Dynamics SL software users, partners, industry experts ...
(Date:11/27/2015)... ... , ... CBD College is proud to announce that on November ... to its Diagnostic Medical Sonography program. CBD College is honored to join this very ... and universities in the state of California make the cut. CBD College is officially ...
(Date:11/27/2015)... ... November 27, 2015 , ... Indosoft ... announces the incorporation of Asterisk 11 LTS (Long Term Support) into its Q-Suite ... LTS brings Q-Suite 5.10 up-to-date with a version of Asterisk that will receive ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... addition of the  "2016 Future Horizons ... Cell Surface Marker Testing Market: Supplier ... to their offering.  --> ... of the  "2016 Future Horizons and ...
(Date:11/25/2015)... 2015  Amgen (NASDAQ: AMGN ) today announced ... the United States (U.S.) Food ... candidate to Humira ® (adalimumab). Amgen believes this ... the FDA and represents Amgen,s first BLA submission using ... , M.D., executive vice president of Research and Development ...
(Date:11/25/2015)... 25, 2015 AAIPharma Services Corp./Cambridge Major ... at least $15.8  Million to expand its laboratories ... . The expansion will provide additional office ... growing demands of the pharmaceutical and biotechnology markets. ... will provide up to 40,000 square feet of ...
Breaking Medicine Technology: