Researchers from Germany recently published a new study that can change how future scientists study the replication of the Dengue and Zika viruses within the human body.
In an article recently published in the American Society for Microbiology’s journal, mBio, researchers from the University of Heidelberg analyzed how human infection with either the Dengue or Zika virus can affect cellular translation.
Dengue and Zika are both known to cause mild illness; however, infection with either of these viruses can sometimes cause severe complications. According to the World Health Organization, “Severe Dengue is a potentially deadly complication due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.” Moreover, infection with the Zika virus during pregnancy can result in fetal death, microcephaly, glaucoma, and other neurological complications in developing fetuses. In adults, a Zika virus infection can cause Guillain-Barré Syndrome, which is classified by damaged nerves.
Both the Dengue and Zika viruses are positive-strand RNA viruses that rely on ribosomes for immediate translation. Translation is a three-step process (initiation, elongation, termination) of reading RNA and essentially writing, or ‘making,’ a protein based on the RNA code. That said, viruses do not carry their own translation machinery and, thus, need to “hijack” a host cell to use its translation machinery (ribosomes) and host’s building blocks (amino acids).
An earlier study conducted by Rutgers University researchers noted that specific RNA viruses, such as poliovirus, hepatitis C, and perhaps a number of other viruses normally “copy themselves by seizing an enzyme from their host cell to create replication factories enriched in a specific lipid,” phosphatidylinositol-4-phosphate (PI4P). However, without PI4P, these viruses “are not able to synthesize their viral RNA and replicate.”
According to the University of Heidelberg researchers, human cells usually trigger what is known as a “stress response” in reaction to infection by a virus. Through this response, cells are able to impede viral replication by blocking protein translation, while also forming stress granules (SGs) from cellular RNAs that had not been translated.
When they examined the cellular RNA activity in liver cells of humans infected with the Dengue virus, the team had previously observed that, although viral infection occurred, SGs were either not formed, or formed “very poorly,” according to a press release. In the new study, the researchers suggested that either limiting translation initiation or limiting elongation can stop protein synthesis.
Through further analysis, the researchers concluded that infection with the Dengue virus “impairs host cell translation at the initiation step but does not alter translation elongation.” The researchers discovered that, essentially, the Dengue virus represses “global protein synthesis,” while viral replication is left ongoing; however, further research is needed in order to understand just how these viruses are able to impede host cell translation. In addition, the researchers noted that the Zika virus suppresses cellular translation in a similar manner to that of Dengue virus, leaving viral protein translation unaffected.
Commenting on the research, Alessia Ruggieri, PhD, one of the lead authors of the study, stated, “These viruses are hijacking many of the host cell translation steps or pathways to favor the production of new virus progeny. But how they are doing this is an open question.”