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PLOS Studies Explore Host Responses to Viral Infection, Febrile Illness Culprits

In PLOS Genetics, an international team describes epigenetic changes — and related gene expression shifts — that persist following successful treatment for hepatitis C virus (HCV), a risk factor for hepatocellular carcinoma (HCC). The researchers used chromatin immunoprecipitation sequencing, RNA sequencing, and other approaches to assess active or repressed chromatin marks in HCV-infected cell lines, to identify HCV-dependent histone modification changes, epigenetic shifts that continued after antiviral treatment, and a gene signature with potential ties to HCC itself. "This epigenetic 'scarring' of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by [direct acting antivirals]," the authors report, pointing to "new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections."

A team from Brazil and Australia characterizes host features found in individuals with acute Chikungunya virus (CHIKV) infections for a paper in PLOS Pathogens. Using real-time RT-PCR and RNA sequencing, the researchers assessed blood samples from dozens of Brazilians with arbovirus-related symptoms compared with samples from 20 healthy control individuals, narrowing in on some 3,500 genes that appeared to coincide with CHIKV levels and viral symptoms. They subsequently considered the CHIKV gene signature alongside available dengue virus infection and rheumatoid arthritis signatures, identifying shared and distinct expression changes across the conditions. "By analyzing the blood transcriptome of adults acutely infected with CHIKV, we were able to provide a detailed picture of the early molecular events induced by the infection," the authors report, adding that their systems biology approach "revealed genes that can be investigated extensively as probable therapeutic targets for the disease." 

For a paper in PLOS One, researchers from the US and Uganda share findings from a retrospective metagenomic analysis of children in Uganda with febrile illness. The team did metagenomic sequencing on blood serum, nasopharyngeal, or stool samples from nearly 100 children treated at Uganda's Tororo District Hospital, including infants, toddlers, and children up to almost five years old. More than half of the 94 children carried Plasmodium falciparum bacteria, for example, while 40 percent had human rhinoviruses A and C. The analysis also uncovered cases involving parvovirus B19, human herpesvirus 5, and rotavirus A, the authors note, and made it possible to put together genome assemblies for new and known orthobunyaviruses and rhinoviruses.