In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans. γδ T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses. However, the roles of γδ T cells in HPAI H5N1 viral infection remain unclear. In this study, we found that γδ T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection. HPAI H5N1 viruses could directly activate γδ T cells, leading to enhanced CD69 expression and IFN-γ secretion. Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate γδ T cells. HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.

Output: γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection


Input: Consider Input: Background: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. Methods: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex-and agematched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. Results: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.

Output: BMC Infectious Diseases Sex-and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study


Input: Consider Input: and double-stranded (ds) RNA act as potent IFN inducing signals and we previously showed that E rns efficiently cleaves these substrates, thereby inhibiting an IFN response that is crucial for successful fetal infection. Considering that a large variety of RNases and DNases require dimerisation to cleave double-stranded substrates, the activity of E rns against dsRNA was postulated to depend on homodimer formation mediated by disulfide bonds involving residue Cys171. Here, we show that monomeric E rns is equally able to cleave dsRNA and to inhibit dsRNA-induced IFN synthesis as the wild-type form. Furthermore, both forms were able to degrade RNA within a DNA/RNA-as well as within a methylated RNA/RNA-hybrid, with the DNA and the methylated RNA strand being resistant to degradation. These results support our model that E rns acts as 'nicking endoribonuclease' degrading ssRNA within doublestranded substrates. This efficiently prevents the activation of IFN and helps to maintain a state of innate immunotolerance in persistently infected animals. Bovine viral diarrhea virus (BVDV), a pestivirus within the family Flaviviridae, occurs throughout the world with far-reaching consequences for animal health and the agricultural economy. Infection of pregnant cows within the first ∼120 days of gestation with a noncytopathic (ncp), but not cytopathic (cp), biotype of BVDV may result in the birth of persistently infected (PI) calves 1-6 . The early time point of fetal infection prior to the development of adaptive immunity and the distinct epitheliochorial placenta of ruminants that is impermeable to antibodies, however, cannot fully account for the successful establishment of persistent infection, because the innate immune defense is operative from the earliest time of fetal development. Therefore, in addition to the establishment of virus-specific B-and T-cell immunotolerance during ontogeny and to the lack of transfer of maternal antibodies to the fetus, the interplay of BVDV with the innate immune response of its host animals might be the most important aspect for the long-term survival of this virus in its host population (for review, see refs 1-6 ). Various pattern recognition receptors (PRR), such as the membrane-bound Toll-like receptors (TLR) or the cytoplasmic RIG-I-like receptors (RLR), activate the synthesis of interferon (IFN) type-I (IFN-α/β) upon detection of viral pathogen-associated molecular patterns (PAMP) 7-9 . IFN is a cytokine involved in the most important innate defense mechanism against virus infection, and most viruses, including the pestiviruses, have developed an enormous variety of strategies to bypass these antiviral effects 5,10-14 . The genome of the enveloped pestiviruses consists of a single-stranded (ss) RNA of positive polarity encoding for a single large polyprotein. Cap-independent translation is started by an internal ribosomal entry site (IRES), and the polyprotein is then further processed by cellular and viral proteases into four structural and at least eight non-structural viral proteins [15] [16] [17] . The N-terminal autoprotease N pro and the structural protein E rns are exclusively present in viruses of the pestivirus genus within the flaviviridae family, and both were implicated to be involved in the evasion of the host's type-I IFN defense 2,17,18 . N pro activates the proteasomal degradation of the interferon regulatory factor (IRF)-3 [19] [20] [21] [22] , and possibly also IRF-7 23 , thus preventing the transcriptional activation of the IFN genes. In this manner, the non-structural protein N pro is able in infected cells to prevent IFN synthesis that is induced by the activation Published: xx xx xxxx OPEN www.nature.com/scientificreports/


Output: Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease OPEN