Coronavirus replication is critically linked to two factors within the early secretory pathway, according to new findings by a team of Dutch researchers that are published June 13th in the open-access journal PLoS Pathogens.
Coronaviruses, a group including the well-known SARS virus, are the causative agents of many respiratory and enteric infections in humans and animals. As with all viruses, virtually every step of their infection cycle depends on host cellular factors.
As the first, most crucial step after their penetration into cells, coronaviruses assemble huge RNA replication "factory" complexes in association with characteristic, newly induced double membrane vesicles. The cellular pathways hijacked by these plus-strand RNA viruses to create these "factories" have thus far not been elucidated.
The researchers, led by Cornelis A. M. de Haan, showed that RNA replication of mouse hepatitis coronavirus (MHV) was inhibited by a drug — brefeldin A — that disrupts the central station in the cell's secretory pathway, the Golgi complex. Consistently, depletion of both the cellular target of brefeldin A, a factor called GBF1, and its downstream target, ARF1, was also shown to negatively affect coronavirus infection.
The researchers conclude that "an intimate association exists between the early secretory pathway and MHV replication." They speculate that, while GBF1 and ARF1 are not involved in the formation of the viral replication structures, they probably play a key role in their maturation or functioning. As this work was limited to the mouse hepatitis coronavirus, an interesting next step would be to study the importance of GBF1 and ARF1 in the replication of other coronaviruses.
Source: Public Library of Science
Related stories:
Discovery may help defang viruses
Researchers may be able to tinker with a single amino acid of an enzyme that helps viruses multiply to render them harmless, according to molecular biologists who say the discovery could pave the way for a fast and cheap method of making vaccines.
New approach, old drug show promise against hepatitis C, research shows
The fight against the liver disease hepatitis C has been at something of an impasse for years, with more than 150 million people currently infected, and traditional antiviral treatments causing nasty side effects and often falling short of a cure. Using a novel technique, medical and engineering researchers at Stanford University have discovered a vulnerable step in the virus' reproduction process that in lab testing could be effectively targeted with an obsolete antihistamine.
Landmark study opens door to new cancer, aging treatments
Researchers at The Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.
Accumulated bits of a cell's own DNA can trigger autoimmune disease
A security system wired within every cell to detect the presence of rogue viral DNA can sometimes go awry, triggering an autoimmune response to single-stranded bits of the cell's own DNA, according to a report in the August 22nd issue of the journal
Cell, a Cell Press publication. The source of that single-stranded DNA is so-called endogenous retroelements—genetic elements accounting for a substantial portion of the genome that can move to new locations using a "copy and paste" mechanism, according to the researchers.
'Silencing' HIV with small bits of RNA
Researchers have shown that they can effectively tackle HIV-1 with small bits of gene-silencing RNA by delivering them directly to infected T cells, the major targets of the virus. While earlier studies had shown such a strategy could fight against many viruses including HIV-1, the new study in mice with human blood cells, so-called humanized mice, is the first to demonstrate an effective approach to systemic delivery in a living animal.
New study finds HIV drug can persist in mothers' milk, increasing risk to them and their babies
A drug commonly used in the developing world to prevent transmission of HIV from mother to child persists in the breast milk and blood of the mothers, putting them and their babies at risk for developing drug-resistant strains of the virus, according to researchers at the Stanford University School of Medicine.
New treatment therapy helps inhibit hepatitis C
Two new studies examine the use of the nucleoside polymerase inhibitor, R1626, to the standard therapy for hepatitis C. The reports appear in the August issue of
Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD).
Newly described 'dragon' protein could be key to bird flu cure
(PhysOrg.com) -- Scientists and researchers have taken a big step closer to a cure for the most common strain of avian influenza, or "bird flu," the potential pandemic that has claimed more than 200 lives and infected nearly 400 people in 14 countries since it was identified in 2003.