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Kucha tea plant (Camellia assamica var. kucha Chang et Wang) is regarded as a mutant variety of wild Pu'er tea plant found in few mountain areas of Yunnan, China. Its fresh young leaves and shoots are picked by the indigenous aborigines in these local areas to prepare an herbal tea for the treatment of common cold empirically. Two extra compounds of relative abundance were detected in Kucha tea in comparison with Pu'er tea, and their chemical structures were identified as chlorogenic acid and theacrine. These two compounds as well as two major compounds, strictinin and caffeine, in Kucha tea were evaluated for their cytotoxicity and inhibitory effects on human influenza virus A/Puerto Rico/8/34 by analyzing viral protein expression and progeny production. No or low cytotoxicity was detected for the four Kucha compounds when their concentrations were below 100 μM. Expression of viral NS1 protein was significantly inhibited by chlorogenic acid, theacrine or strictinin, but not caffeine at a concentration of 100 μM. The relative inhibitory potency was detected as chlorogenic acid < theacrine < strictinin, and both theacrine and strictinin displayed significant inhibition at a concentration of 50 μM. According to a plaque assay, viral progeny production was significantly reduced by theacrine or strictinin, but not by chlorogenic acid or caffeine under the same concentration of 100 μM. It is suggested that theacrine and strictinin are two major ingredients responsible for the anti-influenza activity of Yunnan Kucha tea traditionally used for the treatment of common cold. Image 1 [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Dengue infection is essential for clinical care of patients with acute febrile illness. It has beendemon strated that combining NS1 Ag to an early serologic test improved Dengue diagnosis. If IgM has been extensively evaluated, there are few data about IgA detection in association to NS1. The purpose of these clinical studies was to evaluate the efficiency of combining dengue NS1 Ag and anti-NS1 IgA antibodies for the detection of Dengue infection during the acute phase in Asian populations. Methods & Materials: Evaluated kits were Platelia™ Dengue IgA Capture associated to Platelia™ Dengue NS1 Ag for ELISA part and RDT Dengue IgA/IgG associated to Dengue NS1 STRIP for rapid testing. Sensitivity was performed on 216 samples from patients with clinically confirmed Dengue of 3 Asian countries: Cambodia (n=135), India (n= 31) and Singapore (n=50). Specificity was evaluated on 101 sera from 50 healthy Indian donors and 51 febrile patients from Cambodia for which dengue infection has been excluded. Results: Depending on the population, the sensitivity ranged from 48.5% to 93.3% for Platelia™ Dengue IgA Capture assay versus 48.9% to 90.3% for IgM ELISA and 50% to 100% for the IgA rapid test. When NS1 and IgA tests were combined, the sensitivity reached 93.5% to 98.0% for the ELISAs and 94.1% to 100% for the rapid tests, compared to 94.9% for an "IgM+NS1" combination. The overall specificity of the NS1 and IgA combination in ELISA and rapid test assays were 95,9% and 96,0% respectively. The analysis of NS1 and IgA ELISAs sensitivity related to the sampling time after fever onset in Cambodia population showed that NS1 assay sensitivity was lower and decreased earlier (day 5) in secondary infection than in primary one (day 11). Conclusion: Detection of anti-NS1 IgA efficiently completesNS1 antigen detection in the diagnosis of acute dengue infection in Asian populations. The combination performs as well on ELISA as on rapid test format and demonstrates similar performance to "IgM+NS1". Moreover, IgA appears to be especially useful in secondary infections and has also been described to be indicative of more severe outcome in primary infections. [ABSTRACT FROM AUTHOR]

Objective: The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs. Results: The NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1's effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment. [ABSTRACT FROM AUTHOR]

Background: The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein that plays an important role in virus replication, virulence and inhibition of the host antiviral immune response. In the avian influenza virus or human influenza virus, specific amino acids of NS1 have been shown to be important for the virus to antagonize host antiviral defenses and promote viral replication. However, little research has been reported regarding the swine influenza virus (SIV) NS1 protein. Methods: To study the effects of the key amino acids of NS1, we rescued NS1 mutants (S42P, D92E, and S42P/D92E) of the A/swine/Shanghai/3/2014(H1N1) strain and compared their replication ability and cytokine production as well as the intracellular localization in cultured cells. Results: We found that the S42P and D92E mutation displayed no changes on NS1 nuclear localization. The S42P (but not D92E) mutation suppressed protein synthesis and reduced virus growth properties, and there was an inability to antagonize host cell interferon production and IRF3 activation, which led to high levels of IFN-α and IFN-β production. Conclusion: We conclude that the S42 residue of the NS1 of the A/swine/Shanghai/3/2014(H1N1) strain is the key amino acid in regulating the host IFN response by blocking the activation of IRF3 and thus facilitates virus replication. [ABSTRACT FROM AUTHOR]

Background: Non-structural protein NS1 of influenza A viruses harbours several determinants of pathogenicity and host-range. However it is still unclear to what extent each of its two structured domains (i.e. RNA-binding domain, RBD, and effector domain, ED) contribute to its various activities. Methods: To evaluate the respective contributions of the two domains, we genetically engineered two variants of an H7N1 low pathogenicity avian influenza virus harbouring amino-acid substitutions that impair the functionality of either domain. The RBD- and ED-mutant viruses were compared to their wt- counterpart in vivo and in vitro, notably in chicken infection and avian cell culture models. Results: The double substitution R38A-K41A in the RBD dramatically reduced the pathogenicity and replication potential of the virus, whereas the substitution A149V that was considered to abrogate the IFN-antagonistic activity of the effector domain entailed much less effects. While all three viruses initiated the viral life cycle in avian cells, replication of the R38A-K41A virus was severely impaired. This defect was associated with a delayed synthesis of nucleoprotein NP and a reduced accumulation of NS1, which was found to reach a concentration of about 30 micromol.L− 1 in wt-infected cells at 8 h post-infection. When overexpressed in avian lung epithelial cells, both the wt-NS1 and 3841AA-NS1, but not the A149V-NS1, reduced the poly(I:C)-induced activation of the IFN-sensitive chicken Mx promoter. Unexpectedly, the R38A-K41A substitution in the recombinant RBD did not alter its in vitro affinity for a model dsRNA. When overexpressed in avian cells, both the wt- and A149V-NS1s, as well as the individually expressed wt-RBD to a lesser extent, enhanced the activity of the reconstituted viral RNA-polymerase in a minireplicon assay. Conclusions: Collectively, our data emphasized the critical importance and essential role of the RNA-binding domain in essential steps of the virus replication cycle, notably expression and translation of viral mRNAs. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted by researcher D.L. Akey which reveals 3D structure of West Nile virus accessory protein (WNV NS1) and dengue virus accessory protein (DENV NS1), published within the issue. Topics discussed include hemorrhagic fever caused by flaviviruses including DENV and WNV, remodeling of cell membranes by NS1 viral protein, assembling of NS1 in endoplasmic reticulum (ER) as homodimers, hollow interior of NS1 hexamer and domains composition of NS1 dimers.