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Wound healing in Atlantic spiny dogfish sharks.

Field observations and limited experimental studies indicate that elasmobranchs can repair substantial skin injuries, but the temporal course and cellular composition of wound healing in Atlantic spiny dogfish remain poorly characterized. We conducted an exploratory laboratory study in 20 female Atlantic spiny dogfish (Squalus acanthias) using standardized full-thickness skin wounds monitored by serial photography for 35 days, histological analysis at defined post-injury time points, and pooled single-nucleus RNA sequencing of intact and wounded skin. A continuous neoepithelial layer covered all examined wound beds by Day 1, whereas macroscopic wound area decreased progressively over 35 days and dermal denticles remained absent from the repaired surface. Histological examination showed progressive neoepidermal maturation, basement-membrane reformation, collagen deposition, and granulation-tissue organization, indicating that epithelial coverage preceded restoration of normal skin architecture. Single-nucleus RNA sequencing identified epithelial, stromal, vascular, pigment, neural, and immune-cell populations. T and B cells were detected in intact skin, and their relative abundance, together with that of several other leukocyte populations, increased at Day 1 and generally declined by Day 14. Because samples were pooled by time point, these transcriptomic changes are descriptive. These findings characterize rapid early reepithelialization followed by slower tissue remodeling in Atlantic spiny dogfish and provide a foundation for future comparative studies of elasmobranch skin repair.

Animals↗

Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.

BACKGROUND: Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue. METHODS AND RESULTS: We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value. CONCLUSIONS: These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.

Adolescent↗

Early branchings in the evolution of eukaryotes: ancient divergence of entamoeba that lacks mitochondria revealed by protein sequence data.

Phylogenetic analyses of ribosomal RNA sequences have played an important role in the study of early evolution of life. However, Loomis and Smith suggested that the ribosomal RNA tree is sometimes misleading--especially when G+C content differs widely among lineages--and that a protein tree from amino acid sequences may be more reliable. In this study, we analyzed amino acid sequence data of elongation factor-1 alpha by a maximum likelihood method to clarify branching orders in the early evolution of eukaryotes. Contrary to Sogin et al.'s tree of small-subunit ribosomal RNA, a protozoan species, Entamoeba histolytica, that lacks mitochondria was shown to have diverged from the line leading to eukaryotes with mitochondria before the latter separated into several kingdoms. This indicates that Entamoeba is a living relic of the earliest phase of eukaryotic evolution before the symbiosis of protomitochondria occurred. Furthermore, this suggests that, among eukaryotic kingdoms with mitochondria, Fungi is the closest relative of Animalia, and that a cellular slime mold, Dictyostelium discoideum, had not diverged from the line leading to Plantae-Fungi-Animalia before these three kingdoms separated.

Amino Acid Sequence↗

Application of PCR-RFLP and MASA analyses on 18S ribosomal RNA gene sequence for the identification of three Ginseng drugs.

In order to develop convenient and reproducible methods for the identification of Ginseng drugs at a DNA level, PCR-Restriction fragment length polymorphism (PCR-RFLP) and Mutant allele specific amplification (MASA) analyses were applied, based on differences of the 18S rRNA gene sequence among three Panax species. The PCR product of each species on the 18S rRNA gene was digested with the restriction enzymes Ban II and Dde I. Each fragment gave unique electrophoretic profiles for each species (PCR-RFLP analysis). The extracted DNA of each species was amplified by PCR using a designed species-specific oligonucleotide primer. The expected size of the fragments corresponding to each species were detected only when the optimum temperature and reaction time for annealing and extension were established (MASA analysis). These two analytical methods were carried out on three Ginseng drugs and the same results as in their original plants were obtained. The results suggest that PCR-RFLP and MASA analyses under the established conditions are convenient for identifying three Ginseng drugs. Moreover, to insure completion of the identification, a partial sequence of the plastid gene matK was determined in addition to the 18S rRNA gene. The gene sequences of three Panax species were of 1259 base pairs and that of P. quinquefolius was different from the other two at nucleotide position 102.

Panax↗

Markers of microvascular instability predict severity and survival in idiopathic pulmonary fibrosis.

INTRODUCTION: Most research on idiopathic pulmonary fibrosis (IPF) has focused on the interplay among fibroblasts, the immune system and epithelial cells. There is growing evidence that microvascular dysfunction also plays a role in disease progression, but large human translational studies are lacking. In this research, we aim to identify a proteomic signature of microvascular instability and assess the impact of current therapeutics on the microvasculature. METHODS: Olink proteomic data from patients with IPF were obtained from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=914) and an independent validation cohort (n=366). Among the PFF-PR, 640 patients also have whole-blood RNA sequencing data available. A subset of 79 microvascular-associated proteins was curated, and their associations with disease severity and transplant-free survival were examined. An adaptive least absolute shrinkage and selection operator was used to generate a novel microvascular risk score. RESULTS: Higher plasma levels of five microvascular-associated proteins (SDC1, MMP10, THBS2, HGF and SERPINA5) were associated with lung function and survival in both cohorts. Whole-blood RNA sequencing of patients with microvascular risk revealed enrichment of immune-mediated processes. Patients with higher microvascular risk who were subsequently put on nintedanib in the following year had significantly better 3-year transplant-free survival compared with patients who did not receive antifibrotic intervention (HR 0.56, 95%&#x2009;CI 0.35 to 0.89, p=0.0142). DISCUSSION: Integrative multi-omics analyses suggest that perturbations to microvascular remodelling contribute to disease severity and progression in IPF. This analysis offers a framework for a precision medicine approach for IPF.

Idiopathic pulmonary fibrosis↗

Liver/kidney microsome antibody type 1 and hepatitis C virus infection.

Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney microsome antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5' noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assay-positive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 +/- 11 vs. 50 +/- 11 years) and had higher gamma-globulin levels and liver/kidney microsome antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Recognition of the folding consensus in RNA secondary structures by the topological-filtering method.

Functionally homologous RNA sequences can substantially diverge in their primary sequences but it can be reasonably assumed that they are related in their higher-degree structures. The problem to find such structures and simultaneously satisfy as far as possible the free-energy-minimization criterion, is considered here in two aspects. Firstly a quantitative measure of the folding consensus among secondary structures is defined, translating each structure into a linear representation and using the correlation theorem to compare them. Secondly an algorithm for the parallel search for secondary structures according to the free-energy-minimization criterion, but with a filtering action on the basis of the folding consensus measure is presented. The method is tested on groups of RNA sequences different in origin and in functions, for which proposals of homologous secondary structures based on experimental data exist. A comparison of the results with a blank consisting of a search on the basis of the free energy minimization alone is always performed. In these tests the method shows its ability in obtaining, from different sequences, secondary structures characterized by a high-folding consensus measure also when lower free energy but not homologous structures are possible. Two applications are also shown. The first demonstrates the transfer of experimental data available for one sequence, to a functionally related and therefore homologous one. The second application is the possibility of using a topological probe in the search for precise structural motifs.

Algorithms↗

Crystal structures of the antitermination factor NusB from Thermotoga maritima and implications for RNA binding.

NusB is a prokaryotic transcription factor involved in antitermination processes, during which it interacts with the boxA portion of the mRNA nut site. Previous studies have shown that NusB exhibits an all-helical fold, and that the protein from Escherichia coli forms monomers, while Mycobacterium tuberculosis NusB is a dimer. The functional significance of NusB dimerization is unknown. We have determined five crystal structures of NusB from Thermotoga maritima. In three crystal forms the protein appeared monomeric, whereas the two other crystal forms contained assemblies, which resembled the M. tuberculosis dimers. In solution, T. maritima NusB could be cross-linked as dimers, but it migrated as a monomer in gel-filtration analyses, suggesting a monomer/dimer equilibrium with a preference for the monomer. Binding to boxA-like RNA sequences could be detected by gel-shift analyses and UV-induced cross-linking. An N-terminal arginine-rich sequence is a probable RNA binding site of the protein, exhibiting aromatic residues as potential stacking partners for the RNA bases. Anions located in various structures support the assignment of this RNA binding site. The proposed RNA binding region is hidden in the subunit interface of dimeric NusB proteins, such as NusB from M. tuberculosis, suggesting that such dimers have to undergo a considerable conformational change or dissociate for engagement with RNA. Therefore, in certain organisms, dimerization may be employed to package NusB in an inactive form until recruitment into antitermination complexes.

Amino Acid Sequence↗

Linking MRI radiomics to transcriptomics-based radiosensitivity in lower-grade glioma: A radiogenomic framework.

BACKGROUND: RSI is a transcriptomics-based biomarker associated with radiotherapy outcomes, but its clinical application is constrained by the requirement for tumor tissue and RNA sequencing. This study investigates whether MRI-derived radiomic features can reflect RSI-defined intrinsic radiosensitivity in lower-grade glioma.This addresses a critical gap arising from the limited availability of matched imaging and genomic data in routine clinical practice. METHODS: MRI-derived radiomic features were extracted from FLAIR images of lower-grade glioma patients obtained from TCIA and matched with transcriptomic data from TCGA. A total of 107 patients with both MRI and RNA sequencing data were included in the radiogenomic analysis. Radiomic features were ranked using a Borda-based ensemble feature selection strategy. Five supervised machine-learning classifiers were trained to predict RSI-based radiosensitivity classification, and model interpretability was assessed using SHAP within radiogenomic framework. RESULTS: Classification performance increased with feature number and stabilized at compact subset of 13 radiomic features. Logistic regression showed stable performance with an AUC of 0.82 (95&#xa0;% CI: 0.71-0.93). SHAP analysis indicated that heterogeneity-related texture features were dominant contributors to model predictions, with many associated with the RR phenotype, while others were linked to the RS phenotype. CONCLUSION: An MRI-based radiomic signature enables non-invasive prediction of RSI-defined radiosensitivity in lower-grade glioma. Rather than offering an immediately deployable clinical tool, this study establishes a proof-of-concept radiogenomic framework demonstrating that intrinsic radiosensitivity, traditionally assessed through invasive molecular assays, can be approximated using quantitative imaging features. These findings highlight the potential of imaging-based radiosensitivity assessment and provide a foundation for future radiogenomic investigations.

Lower-grade glioma↗

Detection of transmissible gastroenteritis virus using cDNA probes.

Five cDNA probes prepared from molecular clones representing genomic RNA sequences of the virulent Miller strain of transmissible gastroenteritis virus (TGEV) were used in a dot blot hybridization assay to detect TGEV in cell culture and fecal specimens. Two clones (pA2 and pB4) represent nucleotide base pairs at the 3' terminus of the Miller TGEV genome. The other three clones represent various portions of the 5' end of the E2 gene, which codes for the major surface glycoprotein of TGEV. Each of the 32P-labeled cDNA probes hybridized to the virulent Miller, attenuated Purdue and four field strains of TGEV. The probes detected 200 to 2000 pg of TGEV RNA extracted from density gradient purified virions and did not hybridize RNA from mock-infected cell cultures, porcine rotavirus or antigenically unrelated coronaviruses. The pB4 and Hpa-1600 probes detected TGEV RNA sequences in 79 and 88%, respectively of 34 field samples identified as TGEV positive by the immunofluorescence assay and electron microscopy (EM). The pD24 clone, which is able to differentiate TGEV from the antigenically related coronaviruses, also compared favorably with conventional methods of EM and immunofluoresence for the detection of TGEV in fecal specimens.

Animals↗

Nonhomologous RNA recombination during negative-strand synthesis of flock house virus RNA.

During sequential replicative passages of viral RNA from the nodavirus flock house virus, spontaneous deletion of RNA sequences occurred frequently. Families of deleted RNA molecules were derived from both segments of the bipartite viral genome and found to contain single, double, or triple deletions. These deletions were attributed to template switching by the flock house virus RNA replicase, resulting in recombination between distant sequences and excision of the intervening nucleotides. From sequence analysis of the recombination junctions, we concluded that the process of template switching was influenced by both the primary sequence and the secondary structure of the RNA and that it occurred predominantly during synthesis of RNA negative strands.

Animals↗

In&#xa0;Vivo CRISPR Activation Screening Reveals Chromosome 1q Genes VPS72, GBA1, and MRPL9 Drive Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) frequently undergoes regional chromosomal amplification, resulting in elevated gene expression levels. We aimed to elucidate the role of these poorly understood genetic changes by using CRISPR activation (CRISPRa) screening in mouse livers to identify which genes within these amplified loci are cancer driver genes. METHODS: We used data from The Cancer Genome Atlas to identify that frequently copy number-amplified and up-regulated genes all reside on human chromosomes 1q and 8q. We generated CRISPRa screening transposons that contain oncogenic Myc to drive tumor formation. We conducted CRISPRa screens in&#xa0;vivo in the liver to identify tumor driver genes. We extensively validated the findings in separate mice and performed RNA sequencing analysis to explore mechanisms driving tumorigenesis. RESULTS: We targeted genes that frequently undergo amplification in human HCC using an in&#xa0;vivo CRISPRa screening system in mice, which induced extensive liver tumorigenesis. Human chromosome 1q genes Zbtb7b, Vps72, Gba1, and Mrpl9 emerged as drivers of liver tumorigenesis. In human HCC there is a trend in correlation between levels of MRPL9, VPS72, or GBA1 and poor survival. In validation assays, activation of Vps72, Gba1, or Mrpl9 resulted in extensive liver tumorigenesis and decreased survival in mice. RNA sequencing revealed different mechanisms driving HCC, with Mrpl9 activation altering genes functionally related to mitochondrial function, Vps72 levels altering phospholipid metabolism, and Gba1 activation enhancing endosomal-lysosomal activity, all leading to promotion of cellular proliferation. Analysis of human tumor tissues with high levels of MRPL9, VPS72, or GBA1 revealed congruent results, indicating conserved mechanisms driving HCC. CONCLUSIONS: This study reveals chromosome 1q genes Vps72, Gba1, and Mrpl9 as drivers of HCC. Future efforts to prevent or treat HCC can focus on these new driver genes.

Animals↗

Habitat radiomics predicts occult lymph node metastasis and uncovers immune microenvironment of head and neck cancer.

BACKGROUND: Occult lymph node metastasis (LNM) is a key prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). This study was to establish radiomics models derived from intratumoral, peritumoral, and habitat regions for identifying occult LNM in HNSCC. METHODS: Patients with pathologically confirmed HNSCC from three medical Centers (from March 2014 to April 2024) and The Cancer Genome Atlas (TCGA) were enrolled. Center 1 was split into training (n&#x2009;=&#x2009;330) and internal test sets (n&#x2009;=&#x2009;154), while Center 2 and Center 3 served as the external test set (n&#x2009;=&#x2009;183). Genomic set (n&#x2009;=&#x2009;50) from TCGA and single-cell RNA sequencing set (n&#x2009;=&#x2009;6) from Center 1 were used for biological analysis. We used the intratumoral, peritumoral, and habitat volumes of interest (VOIs) to extract radiomics features, respectively. Based on Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) classifiers, nine radiomics models were built to confirm the optimal predictive performance. The best-performing model, along with clinical-radiologic data, was combined to develop a hybrid model. The log-rank test was used to evaluate the model's prognostic performance. Additionally, bulk and single-cell RNA sequencing were applied for investigating the biological mechanisms underlying the optimal model. RESULTS: The RF-habitat radiomics model showed the best performance, achieving AUCs of 0.835-0.919 across all datasets. Survival analysis further confirmed the prognostic value of the RF-habitat radiomics model. The RF-habitat radiomics model and the hybrid model notably surpassed the clinical model in predictive performance. Moreover, the RF-habitat radiomics model was associated with the abundance level of exhaustion-associated CD8&#x2009;+&#x2009;T cells, uncovering the immune microenvironment characteristics contributing to occult LNM in HNSCC. CONCLUSIONS: The RF-habitat radiomics model demonstrated excellent performance for predicting occult LNM in HNSCC across three cohorts, providing a non-invasive solution for occult LNM. Furthermore, radiogenomic analysis further revealed the biological associations of the model, primarily related to T cell dysfunction.

Humans↗

Spliced leader-associated RNA of trypanosomes. Sequence conservation and association with protein components common to trans-spliceosomal ribonucleoproteins.

A spliced leader-associated (SLA) RNA recently identified in Trypanosoma brucei has been proposed as a U5 RNA analog in trans-splicing, based on in vivo psoralen cross-linking to the spliced leader (SL) RNA and a short stretch of homology to a conserved U5 RNA sequence. Here we show that the SLA RNA is in the form of an RNP containing common proteins that also occur in the known trans-spliceosomal snRNPs of T. brucei, the SL, U2, and U4/U6 snRNPs. Therefore the SLA RNP is a member of a larger family of related RNPs. The immunoprecipitation of the SLA RNA by antibodies against common proteins does not require an association between the SLA RNA and the SL RNP. To identify sequences of potential functional importance and to establish a secondary structure model, we have sequenced the SLA RNA and cloned its gene from a related trypanosomatid, Leptomonas seymouri. A sequence comparison between the T. brucei and L. seymouri SLA RNAs reveals that the U5-homologous sequence element is not conserved.

Animals↗

Phylogenetic analysis based on full-length large subunit ribosomal RNA gene sequence comparison reveals that Neospora caninum is more closely related to Hammondia heydorni than to Toxoplasma gondii.

Since its first description in the late 1980s, Neospora caninum has been recognised as a prominent tissue cyst-forming parasite due to its ability to induce congenital disease and abortion in animals, especially cattle. It is found worldwide and is a cause of significant economic losses for the livestock industry. However, its place within the family Sarcocystidae, like that of several other taxa, remains unresolved. Neospora caninum shares several morphological and life cycle characters with Hammondia heydorni, although it is most commonly thought of as being a close relative of Toxoplasma gondii. This study presents information regarding the phylogenetic relationship of N. caninum to species currently classified into the genus Hammondia, as well as to two strains (RH and ME49) of T. gondii based on the full-length large subunit ribosomal RNA gene. Phylogenetic analyses using two alignment strategies and three different tree-building methods showed that the two species in the genus Hammondia are paraphyletic. Neospora caninum was shown to form a monophyletic clade with H. heydorni instead of T. gondii, which in turn was shown to be most closely related to H. hammondi. The finding that N. caninum and H. heydorni are closely related phylogenetically may aid the elucidation of currently unknown aspects of their biology and epidemiology, and suggests that H. heydorni should be considered in the differential diagnosis of N. caninum from other apicomplexan parasites.

Animals↗

Transcriptional and histopathological profiling of skeletal muscle in Bla/J mice at the stage of dysferlinopathy manifestation.

Dysferlinopathy is a rare muscular dystrophy characterized by chronic muscle damage and ineffective regeneration. While late-stage morphological changes, such as fibroadipose replacement, are well described, the early molecular mechanisms driving muscle fiber loss and regenerative failure at the onset of the disease remain largely uncharacterized. To address this gap, we investigated the skeletal muscles of dysferlin-deficient Bla/J mice during the early manifestation stage (3&#x2005;months of age). This exploratory study aimed to identify primary pathomorphogenetic events by correlating the transcriptomic profile of the tissue with its specific histopathological and ultrastructural alterations. We performed a comparative analysis of the m. gastrocnemius in 3-month-old Bla/J mice versus wild-type controls using RNA sequencing, RT-qPCR, histomorphometry and transmission electron microscopy. The results revealed atrophy and muscle fiber necrosis without the expected induction of Fbxo32 and Trim63 ubiquitin ligases, suggesting ubiquitin-proteasome system-independent muscle mass loss. Furthermore, the absence of Casp3, Bak1, and Bad induction, confirmed by the lack of active caspase-3, excluded apoptosis as the primary death mechanism. A differentiation block in satellite cells was confirmed by the lack of Myf5, Myod1, and Myog induction and a trend toward Tead4 suppression, pointing to an early failure of the reparative program. Exploratory RNA sequencing also identified a suppression of Prkn expression accompanied by LC3B-II-positive autophagosome accumulation. Immunohistochemical and immunofluorescent evaluation of the mitochondrial network (TOMM20) revealed abnormal accumulations and dense clumping, indicating impaired organelle clearance. Furthermore, ultrastructural analysis demonstrated internal organelle damage and the presence of myelin-like structures, consistent with a state of stalled mitophagy. Collectively, this exploratory study demonstrates that early muscle atrophy and myofiber necrosis in dysferlinopathy occur independently of canonical ubiquitin-proteasome and apoptotic pathways. Instead, the disease manifestation stage is structurally characterized by stalled mitochondrial clearance and a delayed regenerative response.

Animals↗

Interaction of immune complexes isolated from hepatitis C virus-infected individuals with human cell lines.

We investigated the interaction of immune complexes (IC) isolated from hepatitis C virus (HCV)-infected individuals with several cell lines that differentially express Fc receptors, and analyzed viral infection by the presence of HCV RNA sequences. Monocytic (U937 and Monomac-6) and lymphocytic (MOLT-4 and Jurkat) cell lines were incubated with interferon- plus phorbol myristate acetate to stimulate the expression of Fc receptors before addition of IC. Cell interaction with IC was monitored by flow cytometry. Positive cell fluorescence was detected in U937 and Monomac-6 cells [mean fluorescence intensity (MFI) 10.56+/-0.8 and 11.60+/-0.8, respectively]. Incubation of cells with monoclonal antibodies against Fc receptors for IgG before addition of IC decreased MFI in both cell lines (U937 2.1+/-0.5, Monomac-6 4.4+/-0.8, P<0.001), indicating that cell-IC interaction through these receptors was inhibited. In particular, the blockage of FcgammaRII was responsible for this effect. No binding of IC with either MOLT-4 or Jurkat cell lines was detected, which correlated with a very low Fc receptor expression. HCV RNA sequences were identified in the cells up to 120 h of post incubation with IC. These results suggest that IC can mediate entry of HCV to both U-937 and Monomac-6 cell lines mainly through the FcgammaRII.

Antigen-Antibody Complex↗