Virus World

Blood transfusion safety is an essential element of public health. Current blood screening strategies rely on targeted techniques that could miss unknown or unexpected pathogens. Recent studies have demonstrated the presence of a viral community (virobiota/virome) in the blood of healthy individuals. Here, we characterized the blood virome in patients frequently exposed to blood transfusion by using Illumina metagenomic sequencing. The virome of these patients was compared to viruses present in healthy blood donors. A total number of 155 beta-thalassemia, 149 hemodialysis, and 100 healthy blood donors were pooled with five samples per pool.

Members of the Anelloviridae and Flaviviridae family were most frequently observed. Interestingly, samples of healthy blood donors harbored traces of potentially pathogenic viruses, including adeno-, rota-, and Merkel cell polyomavirus. Viruses of the Anelloviridae family were most abundant in the blood of hemodialysis patients and displayed a higher anellovirus richness. Pegiviruses (Flaviviridae) were only observed in patient populations. An overall trend of higher eukaryotic read abundance in both patient groups was observed. This might be associated with increased exposure through blood transfusion. Overall, the findings in this study demonstrated the presence of various viruses in the blood of Iranian multiple-transfused patients and healthy blood donors.

Published in Viruses (June 23, 2023):

https://doi.org/10.3390/v15071425 

A protein that is critical in controlling replication of West Nile and Zika viruses—and could be important for developing therapies to prevent and treat those viruses—has been identified by a Georgia State University biologist and his research group.

The researchers found Z-DNA binding protein 1 (ZBP1) is a sensor that plays a significant role in triggering a robust immune response when it detects a viral infection within cells. The Georgia State study, published in the journal Frontiers in Microbiology, found ZBP1 is essential for restricting both West Nile and Zika virus replication, and that it prevents West Nile-associated encephalitis (inflammation of the brain) in mice. The absence of ZBP1 in mice leads to 100 percent mortality when infected with even a non-disease-producing strain of West Nile Virus, the study found. "It's significant because you take a virus that has never been shown to kill anything and if you block this protein the virus will just kill everything," said Mukesh Kumar, assistant professor of biology and senior author of the study. "We discovered that when cells are infected with viruses such as Zika and West Nile, they respond by triggering necroptosis, a form of programmed cell death, via ZBP1 signaling. This inhibits  viral replication  and spread, allowing the immune system to clear the virus."

Kumar said the findings could present new treatment strategies for viruses that can infect the central nervous system by modulating ZBP1 expression. Subsequent research by Kumar's team will explore effectiveness against similar viruses such as Eastern Equine Encephalitis and Powassan virus. West Nile Virus is the leading mosquito-born disease and cause of viral encephalitis in the United States, with more than 50,000 people affected, including 480 cases reported in Georgia, according to the Centers for Disease Control and Prevention. There have been 2,330 associated deaths since it first reached the country in 1999. The Culex species of mosquito responsible for spreading it is common throughout the world.

Zika, which is spread by the Aedes mosquito that has been found as far north as Florida and Texas, can cause serious neurological diseases such as Guillain-Barre syndrome, which causes the body's immune system  to attack the nervous system. Birth defects such as microcephaly, an abnormally small head and brain can result. Most people who get Zika or West Nile don't get sick thanks to the body's natural immune response and may not know they've been infected, meaning their cases probably don't get reported. Of the West Nile cases reported in the U.S., nearly 50 percent invade the nervous system leading to life-threatening or -altering consequences such as encephalitis. Drug treatments are often ineffective once a virus reaches the brain, but Kumar hopes enhancing host ZBP1 expression within the central nervous system could clear the  virus from the brain and prevent severe disease associated with neuroinvasive viral infections such as West Nile and Zika....

Study Published in Frontiers in Microbiology (Sept. 11, 2019):

https://doi.org/10.3389/fmicb.2019.02089

A new technology to produce safer 'hybrid' viruses at high volumes for use in vaccines and diagnostics for mosquito-borne diseases has been developed at The University of Queensland. Researchers from UQ and QIMR Berghofer Medical Research Institute have exploited the benign characteristics of the Binjari  virus—inert to humans—to produce 'dangerous looking' mosquito-borne viruses such as Zika and dengue, but which cannot grow in humans or animals. School of Chemistry and Molecular Biosciences' Dr. Jody Hobson-Peters said the team, led by Professor Roy Hall, began to explore this possibility after discovering new viruses in the lab. "We were originally hoping to gain insights into how mosquito-borne viral diseases evolve—viruses like Zika, yellow fever and dengue," Dr. Hobson-Peters said. "We were also hoping to discover new viruses that might be useful for biotechnology or as biological control agents. "The Binjari virus stood out, and while it grows to very high levels in mosquito cells in the lab, it's completely harmless and cannot infect humans or other vertebrate species. "And it is incredibly tolerant for genetic manipulation, allowing us to swap important genes from pathogenic viruses like Zika, West Nile and dengue into the Binjari genome. "This produces hybrid, or chimeric, viruses that physically appeared identical to the disease-causing viruses under the electron microscope, but were still unable to grow in human or animal cells."

The researchers have effectively developed a new biotechnology platform requiring low biocontainment, to help safely develop vaccines and diagnostics against these mosquito-borne diseases. Professor Andreas Suhrbier, from QIMR Berghofer Medical Research Institute, said the team hoped to push this technology further down the development pathway toward human applications. "The main advantage of this system is that it is safe," Professor Suhrbier said."  "These hybrids cannot infect humans, meaning that manufacture of vaccines and diagnostic reagents don't require the strict and expensive biosecurity infrastructure ordinarily needed to grow these pathogenic viruses." "The research is a testament to collaborative science—this all fell into place, with amazing collaboration within the Australian Infectious Diseases Research Centre. "It's a technology that will truly revolutionise the manufacture of vaccines—supercharging high-volume vaccine development."

Published in Science Translational Medicine (11 December 2019):

https://doi.org/10.1126/scitranslmed.aax7888