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Jun 10 2024 Ruhr University Bochum

If the virus incorporates host genetic segments into its genome, the infection may become chronic.

Why does Hepatitis E become chronic in some patients, and why do medications not work? To find out, an international research team led by scientists from Bochum observed a patient with chronic Hepatitis E infection over a year. Repeated sequencing of the virus RNA showed that the virus incorporated various parts of the host's messenger RNA into its genome. This resulted in a replication advantage, which may have contributed to the infection becoming chronic. The so-called insertion of host RNA can possibly predict the transition of an acute infection to a chronic condition." 

Dr. Daniel Todt, head of the Computational Virology research group, Department of Medical and Molecular Virology, Ruhr University Bochum, Germany

The researchers report in the journal Nature Communications on June 6, 2024. Sequencing of the virus population

Around 20 million people worldwide contract Hepatitis E every year. Normally, the infection heals without consequences, but it can be life-threatening for pregnant women or people with suppressed immune systems. In some cases, it becomes chronic. There are no specific effective medications. The broad-spectrum antiviral drug Ribavirin is also used against Hepatitis E, but it does not always work.

How can the virus evade the immune system? Why does the infection become chronic and not heal? The researchers wanted to find out and analyzed for the first time all virus populations of a chronically infected patient over a period of more than a year. They examined more than 180 individual sequences from blood samples in detail. Replication in cell culture benefits from host RNA

"The Hepatitis E virus has a so-called hypervariable region in its genetic information, into which it can incorporate various RNA sequences from host cells," describes Daniel Todt. His team was able to show that the composition of this region changed massively during the observation period. Additionally, many different compositions occurred simultaneously. In cell culture experiments, it was shown that incorporating host RNA provided a replication advantage: The altered viruses could replicate better than others. "We assume that this is partly responsible for the infection becoming chronic and the therapy failing," says Daniel Todt. Related StoriesNew RNA therapy zilebesiran shows promise in lowering blood pressureEvaluating the efficacy of harmol in treating herpes simplex virus-induced keratitisAging affects immune response and virus dynamics in COVID-19 patients, study finds

The researchers examined the composition of the host RNA incorporated into the virus to determine if there were any common features characterizing the gene segments. "However, we could not detect any meaningful similarities," says Todt. The incorporated gene sequences are predominantly those that are very common in host cells, indicating a random selection.

"Possibly, during Hepatitis E infection, a race between the virus and the immune system occurs in the body," speculates Daniel Todt. If the virus manages to incorporate host RNA before the immune system successfully combats the infection, it may lead to a chronic course. "Host RNA in the viral genome could, in any case, serve as a biomarker in the acute phase of an infection, indicating early on that it is likely to become chronic."

The researchers plan to expand their studies to larger cohorts of patients. Funding

The work was funded by the Federal Ministry of Education and Research as part of the junior research group "VirBio" and by the German Research Foundation. Further funding came from the Federal Ministry of Health, the German Centre for Infection Research and the National Institutes of Health. Source:

Ruhr University BochumJournal reference:

Wißing, M. H., et al. (2024). Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication. Nature Communications. doi.org/10.1038/s41467-024-49219-8.

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BlockFi bankruptcy administrator and DOJ agree to dismiss $35M lawsuit

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BlockFi bankruptcy administrator and DOJ agree to dismiss M lawsuit

BlockFi bankruptcy administrator and DOJ agree to dismiss M lawsuit

BlockFi’s bankruptcy administrator and the DOJ have settled a $35 million crypto asset transfer lawsuit.

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Hard-throwing rookie Misiorowski going to ASG

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Hard-throwing rookie Misiorowski going to ASG

Hard-throwing rookie Jacob Misiorowski is a National League All-Star replacement, giving the Milwaukee Brewers right-hander a chance to break Paul Skenes‘ record for the fewest big league appearances before playing in the Midsummer Classic.

Misiorowski was named Friday night to replace Chicago Cubs lefty Matthew Boyd, who will be unavailable for the All-Star Game on Tuesday night in Atlanta because he is scheduled to start Saturday at the New York Yankees.

The 23-year-old Misiorowski has made just five starts for the Brewers, going 4-1 with a 2.81 ERA while averaging 99.3 mph on his fastball, with 89 pitches that have reached 100 mph.

If he pitches at Truist Park, Misiorowski will make it consecutive years for a player to set the mark for fewest big league games before an All-Star showing.

Skenes, the Pittsburgh Pirates right-hander getting ready for his second All-Star appearance, had made 11 starts in the majors when he was chosen as the NL starter for last year’s All-Star Game at Texas. He pitched a scoreless inning.

“I’m speechless,” said a teary-eyed Misiorowski, who said he was given the news a few minutes before the Brewers’ 8-3 victory over Washington. “It’s awesome. It’s very unexpected and it’s an honor.”

Misiorowski is the 30th first-time All-Star and 16th replacement this year. There are now 80 total All-Stars.

“He’s impressive. He’s got some of the best stuff in the game right now, even though he’s a young pitcher,” said Yankees slugger Aaron Judge, who is a starting AL outfielder for his seventh All-Star nod. “He’s going to be a special pitcher in this game for a long time so I think he deserved it and it’s going be pretty cool for him and his family.”

Carlos Rodón, Carlos Estévez and Casey Mize were named replacement pitchers on the AL roster.

The New York Yankees‘ Rodón, an All-Star for the third time in five seasons, will replace teammate Max Fried for Tuesday’s game in Atlanta. Fried will be unavailable because he is scheduled to start Saturday against the Chicago Cubs.

In his final start before the All-Star game, Rodón allowed four hits and struck out eight in eight innings in an 11-0 victory over the Cubs.

“This one’s a little special for me,” said Rodón, an All-Star in 2021 and ’22 who was 3-8 in his first season with the Yankees two years ago before rebounding. “I wasn’t good when I first got here, and I just wanted to prove that I wasn’t to going to give up and just put my best foot forward and try to win as many games as I can.”

The Kansas City Royals‘ Estévez replaces Texas’ Jacob deGrom, who is scheduled to start at Houston on Saturday night. Estévez was a 2023 All-Star when he was with the Los Angeles Angels.

Mize takes the spot held by Boston‘s Garrett Crochet, who is scheduled to start Saturday against Tampa Bay. Mize gives the Tigers six All-Stars, most of any team and tied for the franchise record.

Royals third baseman Maikel Garcia will replace Tampa Bay‘s Brandon Lowe, who went on the injured list with left oblique tightness. The additions of Estévez and Garcia give the Royals four All-Stars, matching their 2024 total.

The Seattle Mariners announced center fielder Julio Rodríguez will not participate, and he was replaced by teammate Randy Arozarena. Rodríguez had been voted onto the AL roster via the players’ ballot. The Mariners, who have five All-Stars, said Rodríguez will use the break to “recuperate, rest and prepare for the second half.”

Arozarena is an All-Star for the second time. He started in left field for the AL two years ago, when he was with Tampa Bay. Arozarena was the runner-up to Vladimir Guerrero Jr. in the 2023 Home Run Derby.

Rays right-hander Drew Rasmussen, a first-time All-Star, is replacing Angels left-hander Yusei Kikuchi, who is scheduled to start Saturday night at Arizona. Rasmussen is 7-5 with a 2.82 ERA in 18 starts.

San Diego added a third NL All-Star reliever in lefty Adrián Morejón, who replaces Philadelphia starter Zack Wheeler. The Phillies’ right-hander is scheduled to start at San Diego on Saturday night. Morejón entered the weekend with a 1.71 ERA in 45 appearances.

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M’s Raleigh hits 2 more HRs, brings total to 38

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M's Raleigh hits 2 more HRs, brings total to 38

DETROIT — Cal Raleigh hit his 37th and 38th home runs in Seattle‘s 12-3 victory over Detroit on Friday night to move within one of Barry Bonds’ 2001 major league record for homers before the All-Star break.

Raleigh hit a solo homer off former teammate Tyler Holton in the eighth to tie the American League record of 37 before the All-Star break set by Reggie Jackson in 1969 and matched by Chris Davis in 2013.

“[Holton] and I are really good friends, and I’ve caught a lot of his pitches,” said Raleigh, who was in the lineup as the designated hitter instead of at catcher. “I don’t think that helped much, but I’m sure he’s not very happy with me.”

Raleigh hit a grand slam off Brant Hurter in the ninth.

“I didn’t even know it was a record until just now,” Raleigh said. “I don’t have words for it, I guess. I’m just very grateful and thankful.”

It was Raleigh’s eighth multihomer game this season, tying Jackson (also in 1969) for the most such games before the All-Star break in MLB history, according to ESPN Research. He also tied Ken Griffey Jr. for the most multihomer games in Mariners franchise history.

Seattle has two games left in Detroit before the break.

“Cal Raleigh … this is just unbelievable,” Mariners manager Dan Wilson said. “He’s already set the AL record and now he’s only one short of Barry. There are two games, so who knows?”

Raleigh hit 10 homers in March and April, 12 in May, 11 in June and has five in July.

“This is a very boring comment, but baseball is all about consistency,” Wilson said. “This hasn’t been one hot streak, he’s doing this month after month. That says everything.”

The Associated Press contributed to this report.

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