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.

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

Zika virus is an emergent pathogen that gained significant importance during the epidemic in South and Central America as unusual and alarming complications of infection were recognized. Although initially considered a self-limited benign infection, a panoply of neurologic complications were recognized including a Guillain-Barré-like syndrome and in-utero fetal infection causing microcephaly, blindness, and other congenital neurologic complications. Numerous Zika virus vaccines were developed, with nine different vaccines representing five different platforms entered into clinical trials, one progressing to Phase II. Here we review the current landscape and challenges confronting Zika virus vaccine development.
Tropical Medicine and Infectious Disease Zika Vaccine Development-Current Progress and Challenges for the Future

Metagenomics is currently the only generic method for pathogen detection. Starting from RNA allows the assessment of the whole sample community including RNA viruses. Here we present our modular concerted protocol for sample processing for diagnostic metagenomics analysis of human, animal, and food samples. The workflow does not rely on dedicated amplification steps at any stage in the process and, in contrast to published methods, libraries prepared accordingly will yield only minute amounts of unclassifiable reads. We confirmed the performance of the approach using a spectrum of pathogen/ matrix-combinations showing it has the potential to become a commonly usable analytical framework. Diagnostic metagenomics with high-throughput sequencing (HTS) techniques continuously gains importance for broad and swift identification of pathogens in human, animal, and food samples 1 . While for known pathogens, highly sensitive and specific diagnostic methods like real-time quantitative PCR (qPCR) are in routine use and deliver reliable results, the identification of unrecognized pathogens, meaning unexpected or newly emerging pathogens or pathogens that are only distantly related with known ones, can be very difficult. In this respect, metagenomics using HTS are much more promising than routine diagnostics. Unrecognized pathogens, especially newly emerging zoonoses, may cause serious infectious diseases, and a delay of medical treatment or development of vaccines might have fatal consequences for the affected patients and animal stocks. Such delays can be caused by performing numerous laborious screening tests until the potential pathogen is found instead of a single comprehensive screening test. Prominent cases of emerging infectious diseases caused by novel or varying viruses for instance are the discovery of the Middle East respiratory syndrome (MERS) coronavirus in 2012 2 , the tremendous Ebola outbreak in 2014 3 , the report on a novel zoonotic bornavirus 4 , or the detection of the new Schmallenberg virus 5 affecting domestic and wild ruminants. However, infectious diseases with clinical signs like high fever, diarrhoea, or encephalitis − often life-threatening − can be caused by very different infectious agents 6,7 , not only viruses. In such puzzling cases, a generic approach that works likewise successful and efficient for all pathogen groups, as sketched in Fig. 1 , is essential. In a number of review articles 1,8-12 , valuable considerations for this approach have been summarized. In addition to the overall workflow outlined in Fig. 1 , after metagenomic analysis, it is desirable to confirm the initial sequencing-based suspicion by other methods and in the ideal case by fulfilling the Henle-Loeffler-Koch postulates 13 as for example done in case of the Schmallenberg virus 5 . Metagenomics for generic pathogen detection, so-called diagnostic metagenomics, in its pure form is a broad and undirected approach to find gene sequences or sequence fragments of infectious agents within sequence data sets of the whole community of a sample generated by high-throughput sequencing. A crucial point when handling diagnostic sequencing approaches is to explicitly distinguish between i) high-throughput well-standardisable routine diagnostics for expected known pathogens and ii) diagnostic metagenomics for all including unrecognized pathogens. The first approach is easier to design based on the spectrum of known sequences, testing with specific oligonucleotide primers for pathogens of known identity 14,15 , known tropism, and maybe also of a known proportion within a sample. The latter one − used for unrecognized pathogens like in the case of Schmallenberg virus 5 − should be a generic approach that can ideally be applied to all samples and pathogens. This approach can indeed be developed and tested using samples of known origin and pathogen content. In case of an emergency, however, there might be no information about nature and proportion of the pathogen and only clinical data could be available, and the sample is a closed book. For these cases, metagenomics Published: xx xx xxxx OPEN www.nature.com/scientificreports/

A Versatile Sample Processing Workflow for Metagenomic Pathogen Detection OPEN