New Anti-Viral Drug Potential Boon to Aquaculture

Jan. 3, 2017

Washington, DC - January 3, 2017 - A recently developed antiviral drug has been found to inhibit an important pathogen in the world of aquaculture. The compound, which goes by the alphanumeric, LJ001, also holds promise as a vaccine for fish. The research is published in the Journal of Virology, a journal of the American Society for Microbiology.
 
LJ001 reduced IHNV infections—both in fish cells in test tubes, and in experiments in infected rainbow trout fry—in a dose-dependent, time dependent manner, said Hector Aguilar-Carreno, PhD, who is Associate Professor in the Paul G. Allen School for Global Animal Health, Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman.
 
The drug also reduced transmission of the virus, but did not completely block it at established antiviral levels, according to the report. “Therefore, LJ001 may be best suited as a therapeutic for aquaculture settings that include viral infections with lower viral shedding rates than “infectious hematopoietic necrosis virus” (IHNV, a virus from the family Rhabdoviridae, that inflicts huge losses on aquaculture), or where higher viral titers are required to initiate infection of na├»ve fish,” the investigators wrote.
 
The data also suggest that IHNV viruses that have been inactivated by the anti-viral can generate an “innate immune” response. This means that LJ001 might be useful for vaccination approaches. Innate immune response involves certain nonspecific cells of the immune system attacking foreign cells or pathogens.
 
LJ001’s history is somewhat unusual. “Several years ago I was involved in the discovery of a drug that could inhibit a number of viruses,” said Aguilar-Carreno. The drug, which kills viruses that have an envelope, has an odd limitation: it only kills viruses in the presence of light. After some thought, it occurred to Aguilar-Carreno, that the limitation could be transformed into an advantage by applying the drug to viruses infecting fish, since light penetrates water. They tested the drug on the virus, which is known as “infectious hematopoietic necrosis virus” (IHNV).
 
The drug disables the virus by incorporating itself into the viral membrane, in between the lipid layers. Then, photons from the light hit the drug, causing it to generate singlet oxygen radicals. These radicals react with the membrane lipids, altering them chemically in such a way that the membrane can no longer fuse with those of host cells. That prevents the virus from entering the host cells.
 
 “We are now continuing this research by trying to use LJ001 to inactivate the virus that can then be used to vaccinate the fish and protect them from future viral infections,” said Aguilar-Carreno.
 
Because fish, like other vertebrates, can regenerate cell membranes, the drug has very low toxicity.
 
A major advantage of LJ001 is that the likelihood that INHV would develop resistance to it is “extremely low,” said Aguilar-Carreno. Viruses lack their own reproductive machinery, and so must enter the host cells to reproduce. Like other “enveloped” viruses, INHV obtain their membranes from the host as they exit the cell, following reproduction. Each new virus particle buds at the host membrane, coopting a piece of that membrane to use as its own. Since the membrane comes from the host, there is probably no way for viral genes to mutate in a way that would prevent the drug from bollixing the membrane, said Aguilar-Carreno.
 
The need to protect aquaculture against viruses and other pathogens is acute. “There are tremendous losses in aquaculture due to viral infections,” said Aguilar-Carreno. “Many viruses can wipe out entire populations of fish. The aquaculture industry would benefit greatly from either drugs that can combat existing viral infections or from vaccines for viral diseases in aquaculture that are currently untreatable.” There are 11 severe viruses that coopt lipid membranes from host cells, and they infect trout (IHNV), salmon, carp, koi, and shrimp. All are likely susceptible to LJ001, said Aguilar-Carreno.
 
“Eradication of disease is the true goal—as was done for polio—but minimizing disease with the use of drug treatments or vaccines is monumental in preserving species, protecting human health, and helping our economy,” said Aguilar-Carreno.  

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The American Society for Microbiology is the largest single life science society, composed of over 48,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences.
 
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