Hepatitis E virus can also infect kidney cells: Study
They may be less responsive to standard antiviral treatments than liver cells
The hepatitis E virus (HEV) has long been known to infect liver cells, but researchers have now shown it is also able to infect kidney cells, which may be less sensitive to standard antiviral treatments, a new study shows.
“The entire replication cycle of the virus takes place in kidney cells in the same way as in liver cells,” André Gömer, PhD, the study’s co-senior author at Ruhr University Bochum in Germany, said in a university press release.
One of Gömer’s co-authors further explained their findings.
“It could be that in chronic infections, the kidney acts as a reservoir from which the viruses spread again after a supposedly successful treatment,”added Nele Meyer, the study’s co-first author and a PhD student at TWINCORE, the Centre for Experimental and Clinical Infection Research, in Hannover, Germany.
The study, “Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney,” was published in Liver International.
Hepatitis E virus able to infect, replicate in multiple sets of kidney cells
Hepatitis, referring broadly to inflammation of the liver, is most often caused by a viral infection. HEV, the cause of hepatitis E, is most commonly spread through exposure to contaminated drinking water or food.
HEV is one of the most common causes of acute hepatitis, where liver inflammation lasts less than six months, though in some cases the infection can become chronic and lead to severe liver damage.
People with an HEV infection can also experience problems in other organs, including the kidneys and pancreas. It hasn’t been clear whether this is because HEV can also infect cells in other organs, or if other mechanisms might be at play.
To find out, the researchers conducted a series of experiments in lab-grown human kidney cells. They found HEV was able to infect and replicate, or multiply, in all of the five different sets of kidney cells evaluated.
“We have shown that HEV can recapitulate its entire viral replication cycle in several kidney cell lines [in the lab], including viral entry, replication and assembly and release of infectious virus,” the researchers wrote.
In some of the sets of lab-grown kidney cells, HEV replication was comparable to or even higher than that in lab-grown human liver cells.
These data support the idea that the virus may be able to infect the kidneys as well as the liver, and imply that future studies may be able to use lab-grown cells to examine the effects of HEV kidney infection in greater detail, the researchers noted.
Finding may have ‘significant clinical implications for antiviral treatment’
The researchers then treated these lab-grown kidney cell lines with ribavirin, an antiviral treatment sold as Virazole and also as generics that is used off-label for hepatitis E.
They found ribavirin was less effective at blocking HEV replication in certain sets of kidney cells, which showed a weaker reduction in HEV replication than that seen in lab-grown liver cells.
“This is probably due to the significantly different metabolic profiles of the two organs,” Gömer said.
This finding “may have significant clinical implications for antiviral treatment,” the researchers wrote, and may help explain why ribavirin doesn’t always work to eliminate HEV from the body.
The team emphasized further research is needed to validate and expand on these results.
Next, the researchers analyzed blood, stool, and urine samples from nine people with chronic HEV infections at a time when they had not received antiviral drugs for three or more months. These patients had previously failed to respond to ribavirin, or were ineligible for the therapy.
“Due to the prolonged infection that these patients had suffered, with the possible acquisition of viral mutations leading to adoption to the host, they might also have acquired [extra-liver] infection,” the researchers wrote.
Four of these patients tested positive for HEV’s genetic material in all three samples. When the scientists conducted detailed genetic analyses of HEV collected from these different types of biological materials, they found the viral sequence varied depending on the sample type.
The viruses found in the different samples differ significantly from each other. This indicates that the populations have been developing independently of each other for some time and have undergone a kind of evolution in the respective organ.
This finding implies that, when HEV infection occurs, there may be different populations of the virus replicating in different parts of the body, acquiring distinct mutations.
“The viruses found in the different samples differ significantly from each other,” said Patrick Behrendt, PhD, the study’s co-senior author at TWINCORE. “This indicates that the populations have been developing independently of each other for some time and have undergone a kind of evolution in the respective organ.”
Because the kidneys are responsible for filtering out urine, and HEV collected from urine “should originate in the kidney,” the researchers wrote, the findings lend further credence to the notion that HEV can infect the kidneys.
The team noted, however, that they were only able to perform genetic analyses of HEV in urine from a few patients, so further studies will be needed to confirm and validate these findings.
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