Immunofl uorescence microscopy of a chimeric mouse liver repopulated with human hepatocytes. Productive infection of human hepatocytes within a chimeric mouse by hepatitis C virus (HCV) reveals antagonism of the RIGI- like receptor pathway. Due to cleavage of the central adaptor protein MAVS, HCV (green) infected hepatocytes do not exhibit nuclear translocation of the innate immune activating transcription factor IRF3 (red). Evasion of the innate immune system is a central event in HCV establishing chronic infection and inducing hepatocellular carcinoma. Read more about the RIG-I-like receptors signaling in the innate antiviral immunity from the review article wrote by John Errett and Michael Gale (p163-173). (Image courtesy of Nanette Crochet from the Gale laboratory.)
John S. Errett, Michael Gale. Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity[J]. Virologica Sinica, 2015, 30(3): 163-173. doi: 10.1007/s12250-015-3604-5.
Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors (RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns (PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.
Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1 (HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte (CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin (HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.
Taken together with our previous report, current results provide cursory evidence that the sinecatechins’ mechanism of action likely entails some degree of modulation of inflammatory and apoptotic processes, in particular, the NF-κB-pathway. It is possible that sinecatechins also upregulate the host immune response, since the only gene to be significantly upregulated in VR is the pro-lymphocytic IL2; however, further studies are needed to examine the exact pattern of immune regulation. Moreover, since no DEGs were identified in VNR in the prior report, the present study provides putative insight into the expression patterns of patients who are not responsive to sinecatechins.
Our results suggest that TTV is extremely common in the general Chinese population, including infants, providing further evidence that TTV is highly prevalent in the general population worldwide(Mancuso et al., 2013). Furthermore, the overall prevalence of TTV infection based on UTR-PCR in healthy infants, healthy adults, and patients with liver disease was almost 2–3 times higher than that obtained by N22-PCR(p < 0.01, Table 1), which highlights both the considerable influence of the PCR primers on the detection of TTV DNA and the benefits of using UTR-PCR to establish the true overall prevalence of TTV infection. On the other h and , our results also indicate the lack of a clear association of TTV infection with chronic viral hepatitis, which strongly suggests that TTV has little potential for causing hepatitis. However, the virulence and pathogenesis of the different genotypes or strains of TTV remain unclear and require further investigation.
Based on the findings of the present study, we conclude that cats can be infected with human influenza viruses as well as avian influenza viruses. Actually, the recent study has shown that both human-type(α2, 6-linked sialic acid) and avian-type(α2, 3-linked sialic acid)influenza virus receptors were extensively detected in the respiratory organs such as trachea, bronchus, and lung of the domestic cats(Wang et al., 2013). Therefore, cats may act as a vector for human influenza virus transmission within households, posing a potential public health concern. Furthermore, we detected both H5N1 and human virus-seropositive cats in neighboring areas at similar sampling times, suggesting that cats can be simultaneously infected with both avian and human viruses in H5N1 virus-endemic areas. Thus, cats, like pigs, may act as an intermediate host for the emergence of new, potentially p and emic viruses.
In this study, we developed a real-time PCR assay for RHDV detection and quantitation. With this method, the distribution of RHDV in the internal organs and body fluids of infected rabbits was analyzed. The highest viral RNA load was found in the spleen, followed by that in the liver. The virus is shed mainly through the oral, nasal, and urethral routes. Through testing of clinical samples, we found that most farmed rabbits that had been immunized had low levels of RHDV in their tissues. These findings may be useful for further research on the pathogenic mechanism of RHDV and potential RHDV receptors in organs.
In this report, an aquatic birnavirus was isolated from rainbow trout fry, Onhorhynchus mykiss, during a fish health inspection in fish-farms in the west region of Ukraine near the rivers Siret and Cheremosh(Chernivtsi region). Preliminary examination of infected fish revealed a range of lesions, particularly in pancreatic tissue. Morphological changes, such as vacuole enlargement and cell rounding, were caused by viruses in appropriate cell lines. Investigation by electron microscopy demonstrated that the isolated virus was ultrastructurally similar to infectious pancreatic necrosis virus(IPNV). In addition, the nucleotide sequences of the 1120 bp VP2 gene fragments were analyzed and the identity of the isolated IPNV to strain Sp was revealed. The identity of nucleotide sequences was 97%–99%; the isolates of Sp strains most closely related to the Ukrainian IPNV isolate were found in Norway.
Many developing countries lack a functional health care system, especially African countries. Such a system is not only important to monitor emergencies but also to develop an integrated response; otherwise, any epidemic can spread rapidly(as was observed in the case of Ebola) and pose huge problems worldwide. According to WHO reports, the basic health care system in most countries affected by Ebola is very fragile(http://www.who.int/healthsystems); substantial investments are needed to improve the infrastructure and bring reforms. This is not only important for African countries; in fact, most developing countries need additional investments to improve the healthcare sector.