Penn researchers discover new mechanism for viral replication

Aug 16, 2007

Researchers at the University of Pennsylvania School of Medicine have identified a new strategy that Kaposi’s Sarcoma Associated Herpesvirus (KSHV) uses to dupe infected cells into replicating its viral genome. This allows the virus to remain virtually undetected by the body’s immune system. Previous work suggested KSHV needed viral proteins to initiate replication, but this is the first study to directly show that a section of viral DNA can independently draw upon proteins within a host cell to promote its own replication. The study was published in the August issue of Cell Host and Microbe.

“Without the necessary production of a viral protein, the virus goes unidentified by the immune system while utilizing the host cell’s replication machinery,” explains lead author Erle Robertson, PhD, Professor of Microbiology and Director of Tumor Virology Training at Penn’s Abramson Cancer Center. Specifically, KSHV can overwhelm a weakened immune system, resulting in the development of Kaposi’s sarcoma and other diseases of the lymphocytes.

A virus, comprised of only its genetic code wrapped in a protective protein cover, will infect a cell by penetrating its membrane and releasing the viral genome into the cell. Because viruses are asexual, they are dependent upon the replication proteins, or “machinery” of host cells to make new copies of their DNA material. To access the cellular proteins needed to replicate, Robertson says most scientists believed viruses must produce a viral protein.

“Our findings now break the long standing dogma of the virology field, which held that tumor viruses associated with human cancers do require a viral protein to bind and initiate replication,” notes Robertson.

In the Robertson lab, previous studies of human cells infected with KSHV led researchers to locate a gene that codes for a viral protein called latency-associated nuclear antigen (LANA) that binds to viral DNA, signaling initiation of replication. To test whether or not KSHV replication was solely dependent upon LANA, the researchers eliminated the production of LANA by KSHV and introduced the LANA-free expression system into host cells. With viral protein production eliminated, the researchers discovered that KSHV DNA was capable of recruiting the cellular replication machinery proteins and so autonomously replicate.

“Once again, a virus has broken the mold in terms of our understanding of cellular processes and is teaching us new tricks about their ability to utilize the cellular mechanism for replication,” says Robertson. “By studying how viruses usurp this cellular function to their advantage, we can learn new bits of information about the mechanism of cellular replication in humans.”

In the future, Robertson and others plan to explore whether or not other viruses are capable of replicating without utilizing the role of viral proteins and learning more about cellular events that trigger replication. Also, researchers will look to identify ways to block KSHV from replicating without blocking cellular replication in order to stop the virus before it has a chance to overwhelm the immune system and progress into a disease.

Source: University of Pennsylvania School of Medicine

Explore further: Scientists target mess from Christmas tree needles

add to favorites email to friend print save as pdf

Related Stories

Pirate viruses caught in their own trap?

Dec 02, 2014

In order to infect a host cell and proliferate, some viruses, such as the hepatitis C virus, infiltrate the ribosomes, the molecular machines that assemble the proteins present in each of our cells. Viral ...

Computer model enables design of complex DNA shapes

Dec 03, 2014

MIT biological engineers have created a new computer model that allows them to design the most complex three-dimensional DNA shapes ever produced, including rings, bowls, and geometric structures such as icosahedrons that ...

Researchers use ancient gene to study virus biology

Oct 15, 2014

Researchers at the University of Delaware have discovered that an ancient gene—ribonucleotide reductase (RNR), which occurs in all cellular life—provides important biological insights into the characteristics ...

Recommended for you

Scientists target mess from Christmas tree needles

16 hours ago

The presents are unwrapped. The children's shrieks of delight are just a memory. Now it's time for another Yuletide tradition: cleaning up the needles that are falling off your Christmas tree.

Top Japan lab dismisses ground-breaking stem cell study

Dec 26, 2014

Japan's top research institute on Friday hammered the final nail in the coffin of what was once billed as a ground-breaking stem cell study, dismissing it as flawed and saying the work could have been fabricated.

Research sheds light on what causes cells to divide

Dec 24, 2014

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ...

Locking mechanism found for 'scissors' that cut DNA

Dec 24, 2014

Researchers at Johns Hopkins have discovered what keeps an enzyme from becoming overzealous in its clipping of DNA. Since controlled clipping is required for the production of specialized immune system proteins, ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.