Influenza A virus is one of the major human pathogens. The influenza infection can pass out without any subclinical symptoms or infestation can appear in upper respiratory tract as well as in lower respiratory tract where it can result in lethal outcome. Both innate and adaptive immune responses are activated shortly after infection providing protection against infection. Many activities of the cells of innate and adaptive immunity are coordinated by cytokines. However, inordinate or disbalanced immune response may result in overproduction of cytokines as well as chemokines which can lead to severe inflammation, including excessive recruitment of neutrophils and mononuclear cells at the site of infection. These may damage lung tissue, reduce respiratory capacity, and cause severe disease and mortality. Recently, the role of cytokines induced by virus infection has been reevaluated. While moderate inflammatory response protects against development of severe illness, the hyper-inflammatory response can elevate the disease progression. In this mini-review, we summarized the data on cytokines and chemokines induced in the sera of hospitalized patients infected with human and avian influenza viruses and define their possible role in pathogenesis. Interleukin IL-6 and chemokines CCL-2/MCP-1, CCL-4/MIP-1β, CXCL-8/IL-8, CXCL-9/MIG, and CXCL-10/IP-10 are associated with pathogenicity of both avian (H5N1 and H7N9) and human (pdmH1N1 and H3N2) viruses. Chemokines CCL-2/MCP-1, CXCL-8/IL-8, CXCL-9/MIG, and CXCL-10/IP-10 are also related with mortality. These cytokines may be used as targets for new, more complex therapy in the extenuation of unfavorable effects of hyper inflammatory response.

The M2 protein of influenza A viruses forms a proton channel involved in modifying virion and trans Golgi pH during infection. Previous studies of the proton current using whole‐cell patch clamp of mouse erythroleukaemia (MEL) cells expressing the M2 protein of the ‘Weybridge’ strain provided evidence for two protonation sites, one involved in permeation, the other in activation by acid pH. The present report compares the M2 channels of two different strains of influenza virus, ‘Weybridge’ (WM2) and ‘Rostock’ (RM2). Whereas with external acid pH the current‐voltage relations showed similar small degrees of inward rectification, a similar apparent K_d of approximately 10 μm for proton permeation and a high selectivity for protons over Na⁺, the two M2 proteins differed in whole‐cell conductance at low and high pH. The proton conductance of unit membrane area was on average 7‐fold greater in RM2‐ than WM2‐expressing MEL cells. At high external pH WM2 was shown previously to have small conductance for outward current at positive driving potential. In contrast, RM2 shows high conductance for outward current with high external pH, but shows small conductance for inward current with high internal pH, conditions in which WM2 shows high conductance for inward current. The different properties of the conductances due to the two channels at high pH were determined by three amino acids in their transmembrane domains. All intermediate mutants possessed one or other property and transformation of the WM2 phenotype into that of RM2 required substitution in all three residues V27I, F38L and D44N; single substitutions in RM2 effected the opposite phenotypic change. The significance of this difference for virus replication is not clear and it may be that the higher proton flux associated with RM2 is the main factor determining its increased ability to dissipate pH gradients. It is apparent, however, from the specific differences in the sidedness of the pH‐induced changes in voltage dependence of the whole‐cell current that this is an intrinsic property of the virus proton channel which may have parallels with regulation of other proton channels.

The results of biochemical and immunoelectron microscopic studies provide evidence that the NB protein is an integral component of the influenza B virion. Its glycosylation and orientation in the membrane were shown to be equivalent to that of NB in the plasma membrane of virus-infected cells. Sensitivity to proteinase K showed that the N terminus is exterior to the virion and gold immunolabelling of freeze-fractured replicas showed that the C terminus is located in the interior of the virion. The similarities between NB of influenza B and M2 of influenza A viruses in structural features, their presence in the virion and possession of an ion channel activity suggest that, by analogy with the M2 protein, NB may also have a role in virus entry.

Overview of measles and mumps vaccine: origin, present, and future of vaccine production

A short sequence, located between the A14L and A15L open reading frames (ORFs) of vaccinia virus, was predicted to encode a hydrophobic protein of 53 amino acids that is conserved in orthopoxviruses, leporipoxviruses, yatapoxiruses, and molluscipoxviruses. We constructed a recombinant vaccinia virus with a 10-codon epitope tag appended to the C terminus of the A14.5L ORF. Synthesis of the tagged protein occurred at late times and was blocked by an inhibitor of DNA replication, consistent with regulation by a predicted late promoter just upstream of the A14.5L ORF. Hydrophobicity of the protein was demonstrated by extraction into the detergent phase of Triton X-114. The protein was associated with purified vaccinia virus particles and with membranes of immature and mature virions that were visualized by electron microscopy of infected cells. Efficient release of the protein from purified virions occurred after treatment with a nonionic detergent and reducing agent. A mutant virus, in which the A14.5L ORF was largely deleted, produced normal-size plaques in several cell lines, and the yields of infectious intra- and extracellular viruses were similar to those of the parent. In contrast, with a mouse model, mutant viruses with the A14.5L ORF largely deleted were attenuated relative to that of the parental virus or a mutant virus with a restored A14.5L gene.

Interferons lambda, new cytokines with antiviral activity