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Conserved host-exclusive oligonucleotide motifs enriched in pathogenic genes of human oncogenic viruses.

Comparative viral genomics can reveal sequence-level constraints influencing virus-host interactions. Relative minimal absent words (rMAWs) are short oligonucleotide motifs present in viral genomes but completely absent from the host, potentially reflecting selective pressures related to host adaptation and immune evasion. Using the EAGLE algorithm and the GRCh38 human reference genome, we systematically screened for prevalent rMAWs (prMAWs) across six major human oncogenic viruses: Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), human T-cell leukemia virus type 1 (HTLV-1), and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). highly conserved 11- and 12-bp prMAWs were identified in EBV, HBV, HTLV-1, and HHV-8/KSHV, with sequence prevalences ranging from 91.5% to 97.9%. Conversely, no short prMAWs were detected in HCV or HPV, likely reflecting differences in genome architecture, mutation rates, and long-term host adaptation to the human host. Importantly, the identified host-exclusive motifs exhibited non-random genomic distribution and were preferentially embedded within viral genes central to replication, persistence, immune modulation, and oncogenesis, including EBNA-1 (EBV), HBx (HBV), Tax-associated regions (HTLV-1), and lytic replication genes of HHV-8/KSHV. Notably, all detected prMAWs were enriched in GC nucleotides and exhibited marked CpG over-representation, suggesting sequence constraints associated with epigenetic regulation and viral persistence. Collectively, these highly conserved, host-exclusive signatures offer promising, candidates for sequence-directed approaches in the diagnosis, monitoring, and investigation of virus-associated cancers.

Humans

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals

Triacylglycerol metabolism is a novel target to combat West Nile virus infection.

West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.

West Nile virus; lipid

Viral replication through phase separation: Cytosolic and nuclear condensates.

Replication of many RNA and DNA viruses occurs within specialized intracellular hubs organized as membraneless biomolecular condensates (BCs) driven by liquid-liquid phase separation. As obligate intracellular parasites, viruses depend on the host cell machinery to complete their replication cycles and therefore actively remodel the intracellular environment to favor viral genome replication, transcription, and assembly. Cytosolic and nuclear phase-separated replication compartments (RC) provide concentrated and dynamic platforms that promote efficient interactions between viral genomes and viral or host proteins essential for infection. The formation of viral replication BCs is typically facilitated by viral proteins enriched in intrinsically disordered regions and low-complexity domains, which enable multivalent interactions with viral nucleic acids and cellular factors. These interactions are mediated by diverse biophysical forces, including hydrophobic and π interactions, hydrogen bonding, molecular crowding, and osmotic effects. Throughout infection, viral BCs remain highly dynamic, allowing continuous exchange of components and functional maturation of replication hubs. Their properties and activities are further regulated by post-translational modifications of viral and host proteins, such as phosphorylation, acetylation, and methylation. In this review, we summarize current evidence supporting liquid-liquid phase separation as a central organizing principle of viral RCs. We focus on representative RNA and DNA viruses that replicate in the cytosol or nucleus, highlighting virus-specific strategies, conserved mechanisms, and the consequences of BC formation for viral replication efficiency, host antiviral responses, and therapeutic intervention.

Phase Separation

A 4-year longitudinal wastewater surveillance of five gastroenteritis viruses and the correlation with clinical cases in Alberta, Canada.

Viruses are common causes of acute gastroenteritis worldwide. They are detected in large quantities in raw sewage making them amenable to wastewater-based surveillance (WBS). To monitor the prevalence of gastroenteritis viruses in wastewater and assess their correlation with clinical cases, wastewater samples collected between July 2020 and June 2024 from 12 wastewater treatment plants across Alberta, Canada were analyzed for norovirus (NoV) GI & GII, rotavirus (RoV), adenovirus (AdV), sapovirus (SaV) and astrovirus (AsV). Among the 5726 wastewater samples tested, AdV (80.5%) had the highest detection rate followed by NoV GII (75.6%), SaV (63.2%), NoV GI (59.4%), RoV (42.2%) and AsV (20.2%). Winter and spring seasonality was found for NoV and RoV in both wastewater and clinical disease. Public health interventions especially in the 1st year of the COVID-19 pandemic had a significant impact on their burden with marked reduction in wastewater detected viruses and clinical cases. NoV showed a strong correlation between its level in wastewater and the number of clinical cases, while moderate correlation was observed for the other four viruses. Cross-correlation analysis showed that changes of viral RNA concentration in wastewater lagged behind reported gastroenteritis cases by approximately 6 days to 3 weeks. To our knowledge, this is the longest multi-region WBS study monitoring multiple gastroenteritis viruses spanning both COVID-19 pandemic and post-pandemic periods. The data obtained from this study supported WBS as a complementary tool to track population-based circulation of gastroenteritis viruses, providing actionable public health data.

Clinical cases

Metatranscriptomic analysis of viral sequences associated with Culex nigripalpus at an Alabama aquaculture site.

Mosquitoes associated with aquaculture habitats can harbor diverse viruses, yet the viromes of many locally abundant species remain poorly characterized. At an aquaculture-associated site in Auburn, Alabama, we surveyed mosquito populations and found Culex nigripalpus to be the dominant species collected. To characterize viruses associated with this mosquito, we performed RNA-seq on pooled female Cx. nigripalpus and compared complementary bioinformatic workflows for viral detection and genome recovery. One workflow removed host-associated reads by mapping to the closest available mosquito reference genome prior to assembly, whereas a second workflow used fully de novo assembly and viral database annotation. Additional protein-level filtering, cross-workflow comparison, and comparison of Trinity and rnaSPAdes assemblies were used to prioritize well-supported viral candidates. Across the original analyses, 16 submitted accessions corresponding to 12 collapsed virus/name groups were recovered, including Merida virus, Hubei mosquito virus 5, Zhejiang mosquito virus, Hubei virga-like virus 3, Rinkaby virus, Elemess virus, Qingnian mosquito virus, Serbia narna-like virus 2, XiangYun narna-levi-like virus 8, Ecclesville picorna-like virus, and baculovirus-like fragments. Several candidates were supported across multiple workflows, while others were recovered only under specific analytical conditions, indicating that candidate recovery was influenced by assembly and filtering choices. Selected viral contigs were independently supported by RT-PCR amplification. Overall, these results provide a first characterization of viral sequences associated with Cx. nigripalpus from an Alabama aquaculture-associated site and show that comparison across assembly and filtering strategies helped prioritize the most consistently supported viral candidates.

Animals

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (•OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated •OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. •OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of ∼1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. •OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following •OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus

Identification of a novel plant polerovirus in the whitefly Aleuroclava gordoniae.

We report the genome sequence of Aleuroclava gordoniae-associated polerovirus (AgAP), identified from the whitefly Aleuroclava gordoniae. The 5,650-nt AgAP genome contains 6 open reading frames. Phylogenetic analysis places AgAP within the genus Polerovirus, which comprises plant-infecting viruses. This study provides a genomic resource for further investigation of virus-insect associations.

plant virus

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Genetic Diversity of BK Polyomavirus Among Renal Transplant Recipients in Yunnan, China.

BK polyomavirus (BKV) infection, a common complication following kidney transplantation, can lead to BKV-associated nephropathy (BKVN). Molecular genetic studies have classified BKV into four genotypes (I-IV); however, comprehensive molecular characterization of BKV strains circulating in China remains limited. This study aimed to elucidate the predominant subtypes and clinical infection characteristics of BKV strains among kidney transplant recipients in Yunnan, a province in southwestern China. PCR-amplified BKV DNA sequences from kidney transplant recipients were aligned with reference strains and subjected to phylogenetic analysis. The viral VP1 gene was successfully amplified from 180 participants, spanning 16 ethnic groups. Genotype I was the predominant viral strain (56.66%, 102/180), followed by genotype IV (43.33%, 78/180), while genotypes II and III were not detected. Among genotypic subtypes, IVc-1 was most prevalent (40.0%, 72/180), followed by Ic (38.3%, 69/180) and Ib-1 (18.3%, 33/180). IVa-1 and IVa-2 were rare, identified in only 0.6% (n&#x2009;=&#x2009;1) and 2.2% (n&#x2009;=&#x2009;4) of cases, respectively. No significant differences in sex, age, BKVN incidence, BK viremia, or viruria were observed between patients with BKV-I and BKV-IV infections. Among the five confirmed BKVN cases, two were genotyped as subtype Ic, one as Ib-1, and two as IVc-1. Clinical phenotypes were also comparable between patients with BKV-I and BKV-IV infections. This study represents the largest single-center sequencing analysis of BKV in kidney transplant recipients in China, offering a valuable genomic resource for future research.

Humans

Viral community in Aspergillus spp. isolated from commercially available fermented dried bonito.

Katsuobushi is a traditional processed seafood product used in Japanese-style cooking, and when it is produced through fermentation by fungi, it is called karebushi. The fungi involved in katsuobushi fermentation are collectively referred to as katsuobushi molds. We previously discovered seven novel viruses from katsuobushi molds and determined their genome sequences. However, our previous explorations used only nine fungal strains available from culture collections, leaving the diversity of viruses infecting fungi involved in katsuobushi fermentation unclear. Therefore, in this study, we aimed to isolate fungi from commercially available karebushi and clarify the prevalence of viruses in the isolates. Karebushi produced by three manufacturers was obtained, and 30 fungal strains (including Aspergillus spp.) were isolated from each. Double-stranded RNA (dsRNA) fractions were prepared from the mycelia of the isolated strains. Electrophoresis suggested that a relatively high proportion of the isolates harbored dsRNA elements consistent with RNA virus infection (30-70% per manufacturer; 59% overall). Furthermore, dsRNA sequencing identified four novel viruses in isolates of Aspergillus chevalieri and Aspergillus montevidensis: a beny-like virus, a gammapartitivirus, a narnavirus, and a victorivirus, in addition to two previously reported viruses. Notably, this represents the first report of a beny-like virus in Aspergillus spp. This study provides insights into the diversity of viruses infecting fungi involved in katsuobushi fermentation.

Aspergillus

The present and future of nonviral delivery-based genome editing for hereditary hearing loss.

PURPOSE OF REVIEW: This review summarizes nonviral genome-editing delivery platforms for hereditary hearing loss, focusing on lipid nanoparticles (LNPs) and engineered virus-like particles (eVLPs), and discusses their advantages over adeno-associated virus-based delivery, as well as the barriers to clinical translation. RECENT FINDINGS: Recent advances have established LNPs as a clinically advanced nonviral platform, although challenges related to inner ear biodistribution, cell type specificity, endosomal escape, and immunogenicity remain to be addressed. In parallel, eVLPs have undergone substantial technical evolution, progressing from early low efficiency systems to advanced base editor- and prime editor-eVLP architectures that enhance cargo loading and editing efficiency. Extracellular vesicle-based genome editing has also emerged as an additional platform, although issues related to reproducibility, loading efficiency, and scalability remain major hurdles. SUMMARY: Nonviral genome editing platforms expand the therapeutic toolkit for hereditary hearing loss by enabling transient delivery of genome editors with potential safety advantages. Future efforts should focus on characterizing biodistribution and immunogenicity, refining cell type-specific tropism, and establishing scalable manufacturing processes to enable successful clinical translation.

Humans

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to &#x223c;3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA

Characteristics and functions of a cell adhesion molecule PvCadN in Penaeus vannamei during WSSV infection.

Cell adhesion not only maintains the integrity of the organism, but also plays an important role in the immune system, which is involved in modulation in the interaction between host and virus. In this study, a novel cell adhesion molecule from Penaeus vannamei, designated as PvCadN, was investigated. It had the typical molecular characteristics of cadherin family, with multiple extracellular cadherin repeat domains, a transmembrane region, and a conserved &#x3b2;-catenin-binding motif. Pvcadn is expressed ubiquitously across all detected tissues, with the highest transcriptional level in gills. RNA interference-mediated silencing of pvcadn significantly impaired the adhesion ability of shrimp hemocytes. Upon WSSV infection, pvcadn showed a tissue-specific expression pattern, with upregulation in gills and downregulation in hemocytes. Knockdown of pvcadn markedly suppressed the transcription of WSSV immediate-early gene ie1 and replication of the viral genome in vivo, suggesting that PvCadN acted as a potential virus-associated molecule. Furthermore, it was found that PvCadN was regulated by Lv&#x3b2;-catenin, a core molecule in the Wnt signaling pathway that functions in innate immunity, at the transcriptional and protein levels. Silencing of lv&#x3b2;-catenin significantly downregulated pvcadn transcription, and Lv&#x3b2;-catenin bound directly to the Cadherin C domain of PvCadN. In summary, the study revealed that PvCadN was a key cell adhesion molecule involved in WSSV infection, which was regulated by Lv&#x3b2;-catenin. Our findings will provide fundamental data for further investigation into cadherin-mediated immune regulation in shrimp, and offer new insights for the prevention and control of WSSV.

Animals

Culture of infectious human norovirus isolated from live contaminated oysters.

Human noroviruses are a major cause of foodborne outbreaks worldwide. Filter-feeding shellfish, such as oysters, can bioaccumulate these viruses in their digestive tissue when grown in sewage-impacted coastal areas and are often implicated in norovirus foodborne outbreaks. Despite the high sensitivity of current molecular assays, these methods for norovirus detection in shellfish fail to distinguish between infectious and non-infectious particles. Assessing norovirus infectivity in shellfish remains a challenge due to the lack of suitable isolation methods that maintain capsid integrity. In this study, a protocol for isolating infectious norovirus from oyster tissues, based on chloroform-butanol elution and polyethylene glycol concentration (CB-PEG), was optimized for the recovery of human norovirus GI and GII. While CB-PEG method recovered various norovirus GI and GII genotypes, it was less efficient at the genomic level than a protocol based on proteinase K elution (adapted from ISO 15216) and showed genotype-dependent viral recovery rates. By optimizing the flocculation step, we improved the method's compatibility with human intestinal enteroid (HIE) cultures. Using this approach, we successfully quantified infectious norovirus GII.3 titers recovered from artificially-contaminated live oysters. Interestingly, infectious virus was better isolated following a freezing step of the digestive tissues, with titers ranging from 13 to 40 TCID50/mL for positive samples. In conclusion, this study established an optimized methodological approach for the relative quantification of infectious norovirus GII.3 in shellfish, paving the way for future research on viral persistence and inactivation strategies in this foodstuff.

Norovirus

Genome-wide identification and characterization of ABC transporters and their expression in response to saline-alkaline stress and WSSV infection in Fenneropenaeus chinensis.

ATP-binding cassette (ABC) transporters play crucial roles in stress responses across organisms, yet their functions in Fenneropenaeus chinensis remain largely unknown. In this study, we identified 42 FcABC genes (FcABCs) in the F. chinensis genome and analyzed their phylogenetic relationships, gene structures, and chromosomal distributions. Phylogenetic analysis grouped the FcABCs into eight subfamilies (ABCA-ABCH), with conserved motif and domain compositions within each subfamily. Expression analysis showed that several FcABC genes, including FcABCG5, FcABCA1, and FcABCC3, were significantly induced under saline-alkaline stress in gill and hepatopancreas tissues. In contrast, most FcABCs were downregulated after WSSV challenge, though a subset (e.g., FcABCB1, FcABCC1) exhibited early upregulation. Functional validation via RNA interference demonstrated that knockdown of FcABCG5 increased shrimp mortality under saline-alkaline stress. Cis-regulatory element analysis revealed an enrichment of stress- and immune-related elements in FcABC promoters. Protein-protein interaction network predictions indicated potential roles for FcABCs in cholesterol metabolism and organic anion transport. Our findings provide insights into the roles of FcABC genes in stress adaptation and immune defense, offering candidate genes for the breeding of stress-resistant shrimp varieties.

Animals

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5&#x2009;months, 5-year PFS and OS for the whole cohort (n&#x2009;=&#x2009;86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR&#x2009;=&#x2009;3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR&#x2009;=&#x2009;4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n&#x2009;=&#x2009;59; 89.7%-58.3%). OS differed across groups (log-rank p&#x2009;=&#x2009;0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein&#x2013;Barr virus DNA

Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2&#x2009;months to 72&#x2009;years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.

Humans