Among the dermatophytes, the most common pathogen isolated was Tr

Among the dermatophytes, the most common pathogen isolated was Trichophyton rubrum (59.4%), followed in descending order by: Trichophyton mentagrophytes var. interdigitale (16.6%), Trichophyton mentagrophytes

var. mentagrophytes (9.0%), Trichophyton tonsurans (6.8%), Microsporum canis (5.1%) and Epidermophyton floccosum (2.7%). Among the yeast-like fungi, a marked predominance JQ1 nmr of Candida species was observed (86.3%). Scopulariopsis brevicaulis was the most commonly isolated mould (25.2%). The most frequently affected body sites were the toenails (53.9%), followed by the fingernails (19.0%). In children under 15 years of age, glabrous skin was the most commonly affected body site with M. canis as the most frequent causative agent. “
“The aim of this study was to examine the antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in the intermediate learn more and mature development phases. Candida albicans biofilms, previously grown for either 24, 48 or

72 h in 96-well microtitre plates, were treated for 48 h with amphotericin B, caspofungin or posaconazole in increasing concentrations according to the respective minimal inhibitory concentration (MIC) determined for planktonic cells (1–128 × MIC). The biofilms were quantified using the mean optical density (OD) determined by XTT assay. Antifungal activities were expressed as percentage of reduction in OD of drug-treated Celastrol biofilms compared to untreated biofilms.

To test the fungicidal activity of antifungal agents, the unfixed biofilms were scraped off and seeded to Sabouraud agar. Caspofungin and amphotericin B showed higher activity against C. albicans biofilm grown for 24 h and 72 h (≥50% reduction of OD) than biofilms grown for 48 h, whereas posaconazole showed similar, but reduced activity against all phases of C. albicans biofilm (≤50% reduction of OD). Caspofungin at 1–4 × MIC achieved the greatest decrease in the biofilm OD grown for 24, 48 and 72 h, whereas amphotericin B showed dose-dependent activity. However, all tested antifungals failed to reach fungicidal activity in all biofilm development phases. Invasive Candida infections are associated with high morbidity and mortality in immunocompromised and severely ill patients.1 Surgery, long-term admission at intensive care units, broad-spectrum antibiotics and percutaneous intravascular catheters are predisposing factors for the development of invasive Candida infections.2 Colonisation is common and considered a risk factor for invasive Candida infection.3 On the skin, mucosa and inert surfaces of intravascular catheters Candida cells attach, proliferate and may finally form a biofilm of hyphae and densely packed cells embedded within an inert matrix.4,5 Established biofilms are difficult to eliminate and are a source of persistent infections and recurrent fungaemia.

These cells are known to respond to lipid antigens presented with

These cells are known to respond to lipid antigens presented with CD1d (1,2). Upon stimulation, iNKT cells produces copious amount of pro- and anti-inflammatory cytokines. These innate cells modulate the function of other recruited cells at a given site (1–3). Early modulation by iNKT cells might influence the ongoing immune response in the favour of either host or parasite. As iNKT cells are engaged in early events of immune recognition, their interaction

with infected antigen-presenting Enzalutamide in vitro cells may determine the polarized immunity triggered subsequently (1–3). In vivo specificity of iNKT cells is another unexplored and poorly elucidated area (4). Nature and source of their ligands (various lipid, self or nonself?)

have not been studied, even though their role have been well appreciated in development of NKT cells in the mouse model (5). Various iNKT ligands like marine sponge α-galactosylceramide (αGalcer, KRN7000) (6), microbial see more ligand glycosphingolipid (4,7) and microbial α-galactosyldiacylglycerols (7) have been studied. Leishmania donovani parasite expresses several specific lipid ligands that may serve as a potential ligand for CD1d presentation e.g. lipophosphoglycan (LPG), glycoinositol phospholipids (GPIL) etc. LPG has been shown as a ligand of CD1d presentation (8) and it can activate iNKT cell efficiently (8). Enumerating the frequency, phenotype and function of iNKT cells among patients with visceral leishmaniasis (VL) is worth to understand the early immune pathology, particularly at the bone marrow (BM, one of the disease inflicted

site). We subjected the patient with VL to anti-Leishmania therapy and followed them till the completion of therapy. With the resolution of pathology, we quantified these cells and evaluated their phenotype and function. In this study, we recruited 30 freshly diagnosed untreated cases with VL (kala azar) [Age (Mean ± SD, range), 25·90 ± 17·05, 3–70 years; 18 men and 12 women] and admitted to hospital (Balaji Utthan Sansthan, Patna, Bihar) after their informed consent. The study was approved by the AIIMS Ethics Committee (Ref. No. B-11/6.10.2006; 17 October 2006). Methane monooxygenase Samples (peripheral blood and BM aspirates) from consenting patients were collected in heparinized tubes (Becton Dickinson Vacutainer™ sodium heparin, San Diego, CA, USA). BM aspirates were collected to confirm the diagnosis of parasite infection (9) (L. donovani load = no. of patients; +1 = 15, +2 = 12 and +3 = 3). Patients were advised for treatment with amphotericin-B (1 mg/kg body weight for 20 days, AmB/Fungizone; manufactured by Sarabhai Chemicals, India). Blood specimen from healthy family and nonfamily members (HCs, sharing same endemic region; Bihar, n = 17) was taken as control for study.

These data suggest that NOD2 may counteract the pro-inflammatory

These data suggest that NOD2 may counteract the pro-inflammatory response to Lp by decreasing cytokine production at 4 and 24 h and PMN recruitment at 24 h. The mechanism of this early decrease in proinflammatory response by NOD2 to Lp is unknown. One possibility is that through

NVP-AUY922 chemical structure heterotypic association of the caspase-1 recruitment domains, NOD2 protein may inhibit other inflammasomes, such as those containing NAIP5/NLRC4 37. Alternatively, NOD2 may modulate IL-1β production through interaction with RIP2 or TLR-pathway intermediates. Our study is unique in that it is one of the few to do a side-by-side comparison of both NOD1 and NOD2 in a murine infection model. In comparison, other studies demonstrated unilaterally that NOD1 is important in the gastrointestinal and intravenous

immune response to organisms such as L. monocytogenes and Salmonella Pathogenicity Island 1-deficient Salmonella enterica serovar Typhimurium 38, 39. Furthermore, in isolated lung epithelium, Moraxella catarrhalis-induced IL-8 production is in part due to detection by NOD1 40. Although replication selleck products of C. pneumoniae in vitro and clearance of organisms has been shown to be dependent upon NOD1 and NOD2, increased in vivo mortality was only demonstrated in RIP2 kinase-deficient animals 27. Lastly, although no significant phenotype was seen in Lp infection with the NOD2-deficient mouse, its importance has been demonstrated in other mouse pulmonary models of intracellular infections such as M. tuberculosis28, 29. Together, these studies suggest that Adenosine NOD1 and NOD2 regulate distinct aspects of the in vivo immune response to pathogens. DMEM media, L-glutamine, penicillin, and streptomycin were obtained from Invitrogen. FCS was from Hyclone Thermo-Fisher (Waltham, MA, USA). FUGENE HD was from Roche Applied Bioscience (Mannheim, Germany). Buffered charcoal yeast extract components were from Sigma (St. Louis, MO USA) and Difco/BD Biosciences (San Jose, CA, USA). Lp Corby (serogroup 1) and Lp Corby Flagellin

deficient were gifts from K. Heuner 41. Lp, Philadelphia 1 (American Type Culture Collection – ATCC 33152) was stored as previously described 42, 43. NOD1 and NOD2 expression plasmids were a kind gift from Gabriel Nuñez. Legionella were grown in buffered charcoal yeast extract plates and harvested by scraping into PBS. Bacterial concentrations were estimated by correlating OD600 values with CFU counts on agar plates. All experiments were approved by Institutional Animal Care and Use Committee at the University of Washington. Nod2−/− mice (strain designation B6.129S1-Nod2tm1Flv/J) were derived and backcrossed for eight generations as previously described 44. Nod1−/− mice were derived and backcrossed against eight generations of mice as previously described 12. WT control mice were from a C57BL/6 background (Jackson Laboratory, Bar Harbor, ME, USA).

There are scanty reports of meningitis caused by Rhodurorula spp

There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We selleck inhibitor present one such case of meningitis by Rhodutorula glutinis in HIV-infected

patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological

work-up showed that this is the selleck kinase inhibitor first report of R. glutinis isolation from our institute. “
“Chromoblastomycosis is a chronic mycosis that affects the skin and subcutaneous tissues caused by several genera of dematiaceous fungi. There is not a treatment of choice. Thus, tools that help guide clinical practice are fundamental. In this sense, antifungal activity tests in vitro could be useful. However, trials with chromoblastomycosis agents are scarce. The aim of this study was to evaluate both the in vitro susceptibility of 60 chromoblastomycosis agents to five antifungals and the combination of amphotericin B (AMB) and terbinafine (TRB). TRB, itraconazole (ITZ) and ketoconazole (KTZ) were, in this order, the drugs which showed better activity against the chromoblastomycosis agents. The less active drugs were voriconazole (VRZ) and AMB. The more differentiated group was Exophiala spinifera. Cladophialophora carrionii and Fonsecaea spp. are significantly more susceptible to KTZ than Phialophora verrucosa, whereas C. carrionii is significantly more sensitive to VRZ than P. verrucosa and E. spinifera. Assays in this direction allow

Ribonuclease T1 the knowledge of the susceptibility of the causative agents which may help the management of patients with this disease. This study includes the largest number of these agents and of genera found in the literature. “
“Recent studies have shown decreased susceptibility of Candida krusei to amphotericin B (AmB), in addition to its inherent resistance to fluconazole. The susceptibility of C. krusei to AmB was studied in the Parasitology–Mycology laboratory of Grenoble Teaching Hospital, France. Between 2003 and 2011, we analysed 200 C. krusei isolates from 130 patients. The isolates were mainly collected in intensive care, cardio-thoracic and cancer/haematology units. Minimum inhibitory concentrations (MICs) were determined by the E-test method. The modal MIC was 0.5 μg ml−1; the MIC50 and MIC90 (MICs encompassing 50% and 90% of all isolates tested, respectively) were 0.

We thank the staff of the Fetal Medicine Unit and the midwives at

We thank the staff of the Fetal Medicine Unit and the midwives at St. George’s Hospital, and all the patients for their assistance with this study. RD recruited all subjects and together with PN conducted the observations, and maintained the database. RR

helped in the analysis and wrote the first draft with RD. DW performed the statistical analysis. All authors discussed find more the results and implications and commented on the manuscript at all stages. None. None. “
“Please cite this paper as: Wang F, Hu Q, Chen C-H , Xu X-S, Zhou C-M, Zhao Y-F, Hu B-H, Chang X, Huang P, Yang L, Liu Y-Y, Wang C-S, Fan J-Y, Zhang K, Li G-Y, Wang J-H, Han J-Y. The protective effect of cerebralcare granule® on brain edema, cerebral microcirculatory disturbance and neuron injury in a focal cerebral ischemia rat model. Microcirculation 19: 260–272, 2012. Objective:  The purpose of the present study was to explore the protective effects of CG on rat cerebral injury after focal cerebral I /R. Methods:  Male Sprague–Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes followed by reperfusion for 60 minutes or 24 hours. CG (0.4 or 0.8 g/kg) was administrated 90 minutes before ischemia. Brian edema was evaluated selleck by Evan’s blue dye extravasations and brain water content, leukocyte adhesion, and albumin leakage were determined with an upright fluorescence microscope, and neuron damage was assessed by 2,3,5-triphenyltetrazolium

HSP90 chloride staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemistry of caspase-3, p53, p53 upregulated modulator of apoptosis. Results:  Focal cerebral I/R elicited a prominent brain edema, an increase in leukocyte adhesion, and albumin leakage, as well as neuron damage. All the insults after focal cerebral I/R were significantly attenuated by pretreatment with CG. Conclusions:  Pretreatment with CG significantly reduced focal cerebral I/R-induced

brain edema, cerebral microcirculatory disturbance, and neuron damage, suggesting the potential of CG as a prophylactic strategy for patients in danger of stroke. “
“Compromised perfusion of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous injection of ascorbate inhibits platelet adhesion and plugging in septic capillaries. In this study, we hypothesized that ascorbate reduces aggregation of platelets and their surface expression of P-selectin (a key adhesion molecule) in mice. Platelets were isolated from control mice and subjected to agents known to be released into the bloodstream during sepsis (thrombin, ADP or U46619, thromboxane A2 analog). Platelet aggregation was analyzed by aggregometry and P-selectin expression by flow cytometry. Platelet-activating agents increased aggregation and P-selectin expression. Ascorbate inhibited these increases. This inhibitory effect was NOS-independent (LNAME had no effect).

[19] In 1996, Watson et al proposed a six-tiered grading system

[19] In 1996, Watson et al. proposed a six-tiered grading system that is a modification of Wyler’s grading system, mainly by inserting an additional grade between Wyler’s grades II and III.[13] In 2007, Blümcke et al. proposed a clinicopathological classification system

for HS, using the term “mesial temporal sclerosis (MTS)” based on the cluster analysis of semi-quantitative measurements of neuronal loss in CA1–CA4, showing five distinct patterns of hippocampal pathology.[14] Selleck ZVADFMK They found that these patterns were associated with specific clinical histories and/or post-surgical outcome; for example, the age of the initial precipitating injury (IPI) appeared to be an important predictor of hippocampal pathology, as it was younger in patients with MTS types 1a and 1b (<3 years) than those with MTS types 2 (mean 6 years) and 3 (mean 13 years) as well as no MTS (mean 16 years). While successful seizure control was associated with MTS types 1a and 1b, MTS type 3 (EFS) appears to be a predictor of poorer post-surgical seizure outcome. By contrast, Thom et al. found better outcomes for patients with EFS and poorer outcomes

for the no HS group.[20] Such differences in the results among various studies appear to be a major problem in elucidating the clinicopathological correlation check details of mTLE-HS, and seem to be associated, at least in part, with differences in the numbers of patients studied, inclusion and exclusion criteria and the surgical procedure employed, as well as post-surgical follow-up periods. Interobserver reliability would also affect the histological diagnosis and results of each individual study. Recently, the ILAE constituted a task force of neuropathology within the Commission on Diagnostic Methods, trying to establish an international consensus of histological classification of HS using a semi-quantitative Casein kinase 1 scoring system, based on agreement with the recognition of the importance of defining a histopathological

classification system that reliably has some clinicopathological correlation, such as post-surgical seizure outcome and memory impairment.[21] A new classification will be proposed in the near future. Meanwhile, the authors (HM and TH) reviewed surgical specimens obtained from 41 consecutive mTLE patients (male/female = 24/17; age at onset, 14.7 ± 11.7 years; age at operation, 32.8 ± 10.8 years; post-operative follow-up period, 27–253 months) treated by selective amygdalohippocampectomy with or without temporal lobectomy between 1991 and 2010, excluding 7 cases due to insufficient amount of tissue available for histological study. All patients were operated on by one of the authors (TH) in Tottori University, Tokyo Women’s Medical University, and Moriyama Memorial Hospital, Japan. Histological evaluation was performed on formalin-fixed, paraffin-embedded tissue sections stained by HE and KB, as well as a panel of immunohistochemistry for GFAP, vimentin, and neuronal nuclear antigen (NeuN) (Table 2).

In conclusion, we observed that rSj16 could induce regulatory T c

In conclusion, we observed that rSj16 could induce regulatory T cells through immature DC, and the suppressive function was dependent

on the presence of IFN-γ and IL-10. These data give us a new sight on the role of IFN-γ during the early stages of schistosoma infection. Additional work is needed to investigate the molecular mechanisms behind infection modulation by rSj16. This future work will contribute to a better understanding of the immunology in S. japonicum infection and provide efficient therapeutic strategies. This work was supported by grants from National Basic Research Program of China (973 Program) (No. 2007CB513102) to Yong Wang, the National Important Sci-tech Special learn more Projects (No. 2008ZX10004-011) to Yong Wang and the National Science Foundation of China (No. 30972574

and 81000743) to Zhong-Dao Wu. “
“Citation Hwang KR, Choi YM, Kim JM, Lee GH, Kim JJ, Chae SJ, Moon SY. Association of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism with advanced-stage endometriosis. Am J Reprod Immunol 2010 To investigate whether the this website peroxisome proliferator-activated receptor (PPAR)-γ2 Pro12Ala polymorphism is associated with a risk of advanced-stage endometriosis in a Korean population. Methods of study  Case–control study in a collective of 446 patients and 427 controls. The Pro12Ala polymorphism of PPAR-γ2 gene was genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism Bay 11-7085 (RFLP) analysis. Results  The distribution of the PPAR-γ2 Pro12Ala polymorphism was different between the advanced-stage endometriosis group and the control group (non-CC rates were 5.2% for patients with advanced endometriosis and 10.1% for the control group, respectively, P = 0.006). The frequency for the Ala-12 allele variant

was significantly lower in patients with advanced stage of endometriosis (2.7%) than in the control group (5.3%) (P = 0.006). Conclusion  These findings suggest that the PPAR-γ2 Pro12Ala polymorphism is associated with advanced-stage endometriosis in the Korean population. Unlike results from other studies reported so far, the Ala-12 allele may have protective effects against advanced-stage endometriosis in the Korean population. “
“This unit summarizes a combination of methods that can be optimized for measuring toll-like receptor (TLR) function. TLRs serve as primary innate immune sensors and exhibit high specificity towards evolutionarily conserved microbial and viral structures. The unit focuses specifically on TLR4, the principal Gram-negative lipopolysaccharide (LPS) sensor. Methods described include transient transfections, analyses of activation of various promoters in reporter-gene assays, and induction of IL-8 secretion. Other topics that will be briefly discussed include the necessity for the assessment of surface expression of transmembrane receptors (e.g.

7b) Pro-inflammatory stimuli such as LPS[52] and the cytokines T

7b). Pro-inflammatory stimuli such as LPS[52] and the cytokines TNF-α[53] and IL-1[54] have been shown JQ1 mouse to activate NF-κB via the canonical pathway by phosphorylating serines, leading to I kappa B (IκB) degradation and translocation of the NF-κB complex into the nucleus, thereby activating gene expression

of pro-inflammatory cytokines, which augments the pro-inflammatory response in a positive feed-forward loop.[5] The assessed cytokines were also increased but to a lesser degree in the absence of NF-κB activation with LPS treatment alone (Fig. 7a,b). It is therefore plausible that LPS and Pyl A co-administration activates a strong cytokine response, which then further induces NF-κB activation via a feed-forward mechanism. Lipopolysaccharide induces a strong inflammatory response and leads

MK-8669 in vitro to the recruitment of leucocytes.[55, 56] CRTH2 agonists also chemoattract CRTH2-positive leucocytes,[19, 57] including Th2 cells,[19] eosinophils[58] and dendritic cells.[37] The increase in inflammatory cytokines seen with combined injection of both LPS and the CRTH2 agonist Pyl A may be as a result of the increase in infiltrating leucocytes rather than a direct effect on myocytes. Importantly, CRTH2 is also expressed on Th1 cells in the mouse, unlike the human, which is likely to have contributed to the unexpected pro-inflammatory response seen in the mouse. Several murine studies with CRTH2 agonists/antagonists and the use of CRTH2 knock-out mice have shown a pro-inflammatory role for the CRTH2 receptor.[36, 38, 59-63] The CRTH2 agonist DK-PGD2 causes eosinophilia in mouse lung[63] and intra-peritoneal administration of DK-PGD2 causes a two-fold induction of monocyte chemoattractant Janus kinase (JAK) protein-1 and a 25-fold induction of macrophage inflammatory protein-2.[36] Furthermore, in a murine study of FITC-induced inflammation of the skin (a model of contact hypersensitivity), a CRTH2 antagonist was found to significantly reduce the production of the pro-inflammatory cytokines

TNF-α, IL-1β and the chemokines macrophage inflammatory protein-2 and GRO-α.[64] However, no distinction between the Th1 or Th2 type cytokines being modulated was made. Similarly reduced levels of lung IFN-γ, IL-4 and IL-5 have been observed in a mouse model of airway inflammation upon administration of a CRTH2 antagonist.[62] Our finding of increased fetal viability with Pyl A in LPS-treated mice was surprising in view of the shortened time interval from injection to delivery. Although following spontaneous labour there were no surviving pups in the LPS and LPS/Pyl A treatment groups (Fig. 5b). We attribute this to the pups delivering preterm, based on unpublished data showing non-viability at E16 even in the absence of inflammation-induced preterm labour.

Furthermore, differential stromal subset expression of oxysterol

Furthermore, differential stromal subset expression of oxysterol determines B-cell positioning within lymphoid tissue,[40] adding a further level of complexity to the regulation of lymphocyte localization by stromal cells within SLOs. During inflammation or infection, SLO stromal networks have a degree of plasticity. For example

T-cell and B-cell networks grow and remodel[41, 42] accompanied by changes to homeostatic chemokine expression[43] and lymphatics,[44-46] enabling lymphocyte motility. Data have revealed a key role for IL-7-expressing stromal cells in the infection-induced remodelling of murine LN, PLX4032 with lymphatic endothelial cells found to be the major producers of IL-7 using an in vivo IL-7 fate-mapping system and the staining of human LN sections.[35] Importantly, the in vivo ablation of IL-7-expressing stromal cells abolished infection-driven changes in LN architecture, highlighting the crucial role that these cells play in both the development and subsequent remodelling of the LN. Interestingly FRCs are capable of directly modifying LN endothelial cell growth and expansion,[45] suggesting that both stromal–stromal and stromal–leucocyte interactions regulate the processes OSI-906 purchase underlying

the formation and remodelling of lymphoid tissues. In addition to the developmentally imprinted homeostatic tissues discussed above, ‘intermediate’ lymphoid tissues exist that can be considered as somewhere between predetermined and inflammatory lymphoid tissues. Isolated lymphoid follicles (ILFs) Etofibrate are primarily B-cell follicle-containing lymphoid structures that form at predetermined sites along the length of the mesenteric wall of the small intestine.[47] The

ILFs develop from cryptopatches, clusters of LTi cells seen in both mouse[48] and human[49] intestine. As with the LN, LTi–stromal interactions are vital in ILF formation[50] mediated via LTβR signalling,[47, 51] which is aided by the recruitment of naive LTα1β2-expressing B cells.[52] Recent work has also revealed that the cytokine IL-22 may also be involved in the maintenance of ILFs during bacterial-induced inflammation.[53] Mice kept in a specific-pathogen-free environment develop few and small ILFs,[51] whereas infection with Salmonella enterica greatly enlarges individual ILFs, but importantly does not increase their overall number.[54] The ILFs therefore represent a partially programmed lymphoid tissue lying between ectopic and predetermined. Their anatomical location is predetermined and their developmental processes show many similarities to LN expansion, yet their formation is dependent upon environmental signals, namely microbial stimulation.[54, 55] Truly distinct from developmentally encoded lymphoid tissue are ectopic or TLOs, also known as tertiary lymphoid tissue.

Furthermore, mechanistic studies have revealed that virally encod

Furthermore, mechanistic studies have revealed that virally encoded suppressors can act at different steps in the silencing pathway, including Dicer-2 processing and Ago2 slicing [4],

suggesting that indeed, the entire pathway is required for defense. In contrast to RNA viruses, very little is known about the interactions of DNA viruses with the antiviral RNA-silencing machinery, particularly in arthropods. If these Z-VAD-FMK nmr viruses were restricted by the RNAi machinery, the DNA genome could not be targeted directly; rather, RNA transcripts from the viral genome would form structures with double-stranded character that would be recognized and processed by Dicer-2 (Fig. 1A). In Drosophila, a recent study by Bronkhorst et al. [15] found that overlapping bidirectional transcription of the dsDNA virus invertebrate iridescent virus 6 (IIV-6) likely leads to the formation of dsRNA in trans, which

is processed by Dicer-2 into small RNAs. Conversely, small RNAs produced in wild-caught mosquitoes infected with a ssDNA densovirus, which has no overlapping convergent transcripts, map predominantly to the viral RNA transcripts, suggesting that local interactions within a single-stranded RNA strand form dsRNA in cis that are targeted by antiviral RNAi [16]. ICG-001 However, the mechanism by which the insect RNAi pathway restricts infection of DNA viruses remains poorly understood, and is an important subject of future study. Shrimp are arthropods of agricultural and ecological importance, and white spot syndrome virus (WSSV) is a highly pathogenic dsDNA virus that impacts aquaculture and is thought to have caused over $15 billion in losses [17]. It has been demonstrated that sequence-specific long dsRNAs could confer antiviral immunity against WSSV, as well as against the shrimp RNA virus Taura syndrome virus [18]. Moreover, injection of a synthetic siRNA against WSSV VP28, a viral envelope protein, conferred sequence-specific antiviral resistance [19]. Therefore, both long dsRNAs and synthetic siRNAs induce sequence-specific antiviral immunity in shrimp. Whether the shrimp RNAi pathway

naturally targets RNA or DNA viral pathogens remained unclear. However, in this issue of the European Journal of Immunology, Huang and Zhang examine whether the RNAi pathway directs an antiviral immune response against the dsDNA virus WSSV in shrimp [20]. Since a synthetic siRNA designed to target VP28 (vp28-siRNA) Casein kinase 1 is capable of controlling infection, Huang and Zhang first asked whether vp28-siRNA is produced naturally during infection of the shrimp Marsupenaeus japonicus with WSSV. Indeed, vp28-siRNA can be detected by northern blotting and small RNA sequencing of infected tissues. Expression of vp28-siRNA in various shrimp tissues is dependent upon WSSV infection, as the siRNA cannot be detected in tissues where WSSV does not replicate to detectable levels. Thus, vp28-siRNA is a virus-derived small RNA that is generated from WSSV transcripts during infection.