[Optical coherence tomography angiography in diagnosis of changes in macular capillary blood flow in chronic ischemic retinopathy]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike izmenenii kapillyarnogo krovotoka makuly pri khronicheskoi ishemicheskoi retinopatii.

PURPOSE: Assessment of the indices of macular capillary blood flow and subfoveal choroidal thickness (SCT) using optical coherence tomography angiography in patients with retinal manifestations of ocular ischemic syndrome (RMOIS) associated with atherosclerotic internal carotid artery stenosis. MATERIAL AND METHODS: The study included 34 patients (68 eyes): 21 men, 13 women with RMOIS in one eye. All patients were divided into 2 groups depending on the severity of atherosclerotic internal carotid artery stenosis and ophthalmoscopic picture of the fundus. To obtain objective information we analyzed the degree of decrease in the main indices characterizing macular microcirculation and SCT depending on the severity of RMOIS. RESULTS AND DISCUSSION: Analysis of the results showed relationship between the severity of RMOIS and the deficit in macular microcirculation. The macula of the patients with mild RMOIS was characterized by a decrease in the density of superficial vascular plexus (SVP) and the density of deep capillary plexus (DCP) by 13.5% and 10.5% compared to the controls, respectively; in moderate RMOIS - by 19.7% and 14.6%; in severe RMOIS - by 35.9% and 28%, respectively. With an increase in the severity of RMOIS, the area of the foveal avascular zone increased too: in mild degree RMOIS - by 19%, in moderate - by 38.6%, in severe - by 51%. In proportion to the severity of RMOIS, SCT was reduced: in mild degree RMOIS - by only 8%, in moderate - by 22%, and in severe - by 29.8% of the control. CONCLUSION: The conducted research indicates that pathological changes in RMOIS extend to the entire capillary network of the macula and SCT. With increase in the degree of RMOIS, ischemic changes in all capillary layers of the central parts of the retina proportionally increase in comparison with the control group by 1.15 times in mild degree, by 1.24 times in moderate degree, and by 1.5 times in severe RMOIS.

Inside and outside of virus-like particles HBc and HBc/4M2e: A comprehensive study of the structure.

Hepatitis B virus core antigen (HBc) with the insertion of four external domains of the influenza A M2 protein (HBc/4M2e) form virus-like particles whose structure was studied using a combination of molecular modeling and cryo-electron microscopy (cryo-EM). It was also shown that self-assembling of the particles occurs inside bacterial cells, but despite the big inner volume of the core shell particle, purified HBc/4M2e contain an insignificant amount of bacterial proteins. It was shown that a fragment of the M2e corresponding to 4M2e insertion is prone to formation of amyloid-like fibrils. However, as the part of the immunodominant loop, M2e insertion does not show a tendency to intermolecular interaction. A full-atomic HBc-4M2e model with the resolution of about 3 Å (3.13 Å for particles of Т = 4 symmetry, 3.7 Å for particles of Т = 3 symmetry) was obtained by molecular modeling methods based on cryo-EM data.

Old dog, new tricks: Influenza A virus NS1 and in vitro fibrillogenesis.

The influenza NS1 protein is involved in suppression of the host immune response. Recently, there is growing evidence that prion-like protein aggregation plays an important role in cellular signaling and immune responses. In this work, we obtained a recombinant, influenza A NS1 protein and showed that it is able to form amyloid-like fibrils in vitro. Using proteolysis and subsequent mass spectrometry, we showed that regions resistant to protease hydrolysis highly differ between the native NS1 form (NS1-N) and fibrillar form (NS1-F); this indicates that significant structural changes occur during fibril formation. We also found a protein fragment that is capable of inducing the process of fibrillogenesis at 37 °C. The discovery of the ability of NS1 to form amyloid-like fibrils may be relevant to uncovering relationships between influenza A infection and modulation of the immune response.

Cold and distant: structural features of the nucleoprotein complex of a cold-adapted influenza A virus strain.

Two influenza A nucleoprotein variants (wild-type: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance between nucleoprotein complex strands. The isolated complexes of two ribonucleoprotein variants were characterized by transmission electron microscopy and differential scanning fluorimetry (DSF). Presence of the E292G substitution was shown by DSF to affect nucleoprotein complex melting temperature. In the filament interface peptide model, it was shown that the peptide corresponding in primary structure to the wild-type NP (SGYDFEREGYS) is prone to temperature-dependent self-association, unlike the peptide corresponding to E292G substitution (SGYDFGREGYS). It was also shown that the SGYDFEREGYS peptide is capable of interacting with a monomeric nucleoprotein (wild type); this interaction's equilibrium dissociation constant is five orders of magnitude lower than for the SGYDFGREGYS peptide. Using small-angle neutron scattering (SANS), the supramolecular structures of isolated complexes of these proteins were studied at temperatures of 15, 32, and 37 °C. SANS data show that the structures of the studied complexes at elevated temperature differ from the rod-like particle model and react differently to temperature changes. The data suggest that the mechanism behind cold adaptation with E292G is associated with a weakening of the interaction between strands of the ribonucleoprotein complex and, as a result, the appearance of inter-chain interface flexibility necessary for complex function at low temperature.Communicated by Ramaswamy H. Sarma.

[Functional rehabilitation of patients after endovitreal surgery of rhegmatogenous retinal detachment with complete retinal attachment]. / Otsenka rezul'tatov primeneniya novogo farmakoterapevticheskogo podkhoda v funktsional'noi reabilitatsii patsientov posle endovitreal'noi khirurgii regmatogennoi otsloiki setchatki s polozhitel'nym anatomicheskim rezul'tatom.

Rhegmatogenous retinal detachment (RRD) is one of the most severe eye diseases typically occurring in people of working age. The annual rates of primary vision disability in patients with RRD is 2-9%. PURPOSE: To increase the functional effectiveness of endovitreal surgery in patients with RRD by including Cytoflavin in the system of postoperative rehabilitation. MATERIAL AND METHODS: The study involved 68 patients with RRD aged 37 to 65 years. Patients underwent vitrectomy using the 25 Gauge technology with endolaser coagulation of rupture zones and silicone oil tamponade in the vitreous cavity. Three months after the surgery, silicone oil was removed from the vitreous cavity. Patients were divided into 2 groups: the main - 34 people who received Cytoflavin in addition to standard therapy, and the control - 34 people receiving only standard postoperative treatment. The time course of the treatment's functional effectiveness was analyzed using best corrected visual acuity (BCVA) and macular photosensitivity. Laser Doppler flowmetry (LDF) was used to register the microcirculation and microcirculation efficiency indices. Morphological signs of macular ischemia were registered by optical coherence tomography angiography (OCT-A). RESULTS: Patients of the main group showed higher level of restoration of macular function compared with the control group. The increase in functional activity of the macular area correlated with postoperative dynamics of restoration of central retinal thickness. Analysis of LDF and OCT-A indices showed that improvement of visual functions in patients treated with Cytoflavin is directly related to restoration of chorioretinal blood flow. CONCLUSION: The use of Cytoflavin in patients after endovitreal surgery of RRD led to improvement of BCVA by an average of 2.6 times and photosensitivity of the macula by 2 times. The visual functions of patients improved after using Cytoflavin due to its positive effect on chorioretinal microcirculation and the density of macular capillary plexuses.

[Herpesviral infection as an etiological factor of acute idiopathic optic neuritis]. / Gerpes-virusnaia infektsiia kak étiologicheskii faktor ostrogo idiopaticheskogo opticheskogo nevrita.

PURPOSE: To assess the etiological significance of herpesviral infection (HVI) in patients with acute idiopathic optic neuritis (ON) using clinical and laboratory monitoring. MATERIAL AND METHODS: Clinical and laboratory examinations were conducted for 10 years and were based on the results of etiological monitoring of 79 patients (85 eyes) with acute idiopathic ON in the period of 2005-2015. RESULTS: During a complex examination of 79 patients with acute idiopathic ON, various infectious pathogens were diagnosed in 75 people (94.9±2.1%). HVI was clearly dominant (69 patients - 87.3±2.4%). These patients were divided into 3 etiological groups. The first group - 34 people with herpesviral monoinfection; the second group - 15 people with mixed viral-viral infections; the third group - 20 people with mixed viral-bacterial infections. In the general population of patients with acute idiopathic ON associated with HVI, herpes simplex virus-1 is the most frequent (by more than 2.5 times), the infections of Epstein-Barr virus and cytomegalovirus were detected less often (p<0.05). Active current HVI in the general group of patients was diagnosed in 58 patients (84%). At the same time, reactivation of chronic infection (79.7%) was noted to be prevalent, while primary acute HVI was diagnosed rarely (4.3%). The remaining 11 patients (16%) had chronic persistent HVI. CONCLUSION: Clinical and laboratory monitoring of HVI in patients with acute idiopathic ON has shown the etiological role of herpesviruses in its development. Based on a complex of serological markers in enzyme-linked immunoassay reactions of blood serum, it was found that in patients with acute idiopathic ON the frequency of herpesviral infection is 87.3±2.4%. The proportion of active (etiologically significant) herpesviral infection is 84% of the total group. The results of the clinical and laboratory studies are of great practical importance for verification of the etiologic diagnosis and selection of adequate etiopathogenetic therapy in patients with acute idiopathic ON associated with HVI.

CROSS-PROTECTIVE PROPERTIES OF AN INFLUENZA VACCINE BASED ON HBC4M2E RECOMBINANT PROTEIN.

One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.

[Optic nerve pathology in the structure of diagnostic errors inpatients referred for cataract surgery]. / Patologiyazritel'nogo nerva v strukture diagnosticheskikh oshibok pri napravlenii patsientov na khirurgicheskoe lechenie katarakty.

AIM: to study the frequency of misdiagnosis of cataract in patients with optic nerve pathology or amblyopia and to identify its main causes. MATERIAL AND METHODS: The study enrolled 381 patients (381 eyes) wrongly diagnosed with cataract. A standard set of eye tests was performed. In-depth examination of the macular area was done through biomicroscopy with contactless aspheric lenses of 60 and 90 D. Part of the patients underwent optical coherence tomography and static perimetry as well as examination of electrical sensitivity threshold and electrical lability of the optic nerve. RESULTS: In 190 patients (190 eyes - 49.9%), the true cause of central vision impairment was optic nerve pathology associated with its partial atrophy of different origins: vascular (77.8%) or post-traumatic (22.2%). Glaucomatous atrophy of the optic nerve was found in 175 patients within the age range from 57 to 70 years (175 eyes - 45.9%). These were newly diagnosed cases of advanced open-angle glaucoma. In 16 eyes (4.2%), the true cause of low vision appeared to be amblyopia of some type: strabismic (9 eyes - 56.3%), refractive (4 eyes - 25%), or mixed (3 eyes - 18.7%). CONCLUSION: The main diagnostic errors of attending ophthalmologists were the following: underestimation of the discrepancy between low visual functions and small degree of lens opacity as well as the neglect of careful examination of the fundus (specifically, the optic disc and macula), additional perimetry, thorough history taking, and cover-testing for suspected amblyopia.

COMPARISON OF INFLUENZA A VIRUS INHIBITION IN VITRO BY SIRNA COMPLEXES WITH CHITOSAN DERIVATIVES, POLYETHYLENEIMINE AND HYBRID POLYARGININE-INORGANIC MICROCAPSULES.

Anti-influenza drugs and vaccines have a limited effect due to the high mutation rate of virus genome. The direct impact on the conservative virus genome regions should significantly improve therapeutic effectiveness. The RNA interference mechanism (RNAi) is one of the modern approaches used to solve this problem. In this work, we have investigated the antiviral activity of small interfering RNA (siRNA) against the influenza A/PR/8/34 (H1N1), targeting conserved regions of NP and PA. Polycations were used for intracellular siRNA delivery: chitosan's derivatives (methylglycol and quaternized chitosan), polyethyleneimine, lipofectamine, and hybrid organic/non-organic microcapsules. A comparative study of these delivery systems with fluorescent labeled siRNA was conducted. The antiviral activity of three small interfering RNAs targeting the NP (NP-717, NP-1496) and PA (PA-1630) influenza A viruses genes was demonstrated, depending on the chosen carrier. The most effective intracellular delivery and antiviral activity were observed for hybrid microcapsules.

[Objective method to recognize warning signs in peripheral vitreoretinal dystrophies]. / Sposob opredeleniya priznakov prognosticheskoi opasnosti perifericheskikh vitreoretinal'nykh distrofii.

AIM: to compare the effectiveness of biomicroscopy (BMS) and optical coherence tomography (OCT) in recognizing prognostically unfavorable signs in peripheral vitreoretinal dystrophy (PVRD) patients. MATERIAL AND METHODS: A total of 131 cases of equatorial PVRD (91 eyes of 56 patients) were assessed. The mean patient's age was 24.7 years. The length of the anterior-posterior axis of the eyeball averaged 25.36±1.12 mm. Prevalence of particular warning signs in PVRD patients at BMS or OCT was comparatively analyzed. RESULTS: In 46 eyes with lattice dystrophy it was difficult to determine the presence of vitreoretinal traction at BMS; at OCT, areas of retinal adhesion to the posterior hyaloid membrane (PHM) along the edges of PVRD zones were revealed in all eyes. Of 31 eyes with «snail tracks¼ defects of the retina, 6 were diagnosed at BMS; in OCT scans of these patients, the PHM appeared firmly fixed along the edges of PVRD zones in all cases. As to horseshoe retinal tears (valve-like tears), BMS allowed to visualize vitreoretinal tractions in 7 of 12 eyes, while OCT revealed a tight contact between the PHM and the apex of the retinal flap in 11 of 12 eyes. In 7 eyes with retinoschisis we failed to detect any retinal traction at either BMS or OCT. In «non-differentiable¼ PVRD, BMS was also not able to reveal any vitreoretinal traction, while OCT was - in all 12 cases. CONCLUSION: OCT has proved much more effective than BMS in recognizing prognostically unfavorable signs in particular clinical forms of PVRD, such as vitreoretinal tractions, retinal defects, and intraretinal cavities.

The influenza A virus NS genome segment displays lineage-specific patterns in predicted RNA secondary structure.

BACKGROUND: Influenza A virus (IAV) is a segmented negative-sense RNA virus that causes seasonal epidemics and periodic pandemics in humans. Two regions (nucleotide positions 82-148 and 497-564) in the positive-sense RNA of the NS segment fold into a multi-branch loop or hairpin structures. RESULTS: We studied 25,384 NS segment positive-sense RNA unique sequences of human and non-human IAVs in order to predict secondary RNA structures of the 82-148 and 497-564 regions using RNAfold software, and determined their host- and lineage-specific distributions. Hairpins prevailed in avian and avian-origin human IAVs, including H1N1pdm1918 and H5N1. In human and swine IAV hairpins distribution varied between evolutionary lineages. CONCLUSIONS: These results suggest a possible functional role for these RNA secondary structures and the need for experimental evaluation of these structures in the influenza life cycle.

[INTERACTION OF THE DYE CONGO RED WITH FIBRILS OF LYSOZYME, BETA2-MICROGLOBULIN AND TRANSTHYRETIN].

By means of spectrophotometric assay we investigated interaction of the dye Congo red (CR) with fibrils of model proteins--hen egg white lysozyme, recombinant human beta2-microglobulin (b2M) and recombinant human transthyretin (TTR). The commercial dye sample was found to contain a significant amount of impurities. Methods for the dye purification are disclosed and CR molar extinction coefficient at 490 nm (ε490) was determined to be 3.3 x 10(4) M(-1) x cm(-1) at pH above 6.0. Formation of the CR-fibril complex results in changes in the dye visible absorption spectrum. According to the data on titration of fibril solutions with excess of the dye, CR binds to lysozyme fibrils at a ratio of about 5 molecules per protein monomer within fibril structure, to b2M fibrils--about 4 molecules per monomer, to TTR fibrils--about 4 molecules per subunit of the protein.

[Adenosine A2A receptor as a drug target for treatment of sepsis].

Sepsis is a generalized infection accompanied by response of the body that manifests in a clinical and laboratory syndrome, namely, in the systemic inflammatory response syndrome (SIRS) from the organism to the infection. Although sepsis is a widespread and life-threatening disease, the assortment of drugs for its treatment is mostly limited by antibiotics. Therefore, the search for new cellular targets for drug therapy of sepsis is an urgent task of modern medicine and pharmacology. One of the most promising targets is the adenosine A(2A) receptor (A(2A)AR). The activation of this receptor, which is mediated by extracellular adenosine, manifests in almost all types of immune cells (lymphocytes, monocytes, macrophages, and dendritic cells) and results in reducing the severity of inflammation and reperfusion injury in various tissues. The activation of adenosine A(2A) receptor inhibits the proliferation of T cells and production of proinflammatory cytokines, which contributes to the activation of the synthesis of anti-inflammatory cytokines, thereby suppressing the systemic response. For this reason, various selective A(2A)AR agonists and antagonists may be considered to be drug candidates for sepsis pharmacotherapy. Nevertheless, they remain only efficient ligands and objects of pre-clinical and clinical trials. This review examines the molecular mechanisms of inflammatory response in sepsis and the structure and functions of A(2A)AR and its role in the pathogenesis of sepsis, as well as examples of using agonists and antagonists of this receptor for the treatment of SIRS and sepsis.

[The pathochemical characteristics of oligomeric forms of Tamm-Horsfall protein under urolithiasis].

The role of Tamm-Horsfall protein in pathogenesis of urolithiasis was analyzed. The study of oligomeric forms of protein was carried out using technique of dynamic light scattering. The sampling of 57 patients with urolithiasis and 51 patients of control group of comparative age and gender were examined. The degree of purification of Tamm-Horsfall protein was controlled using denaturant electrophoresis in polyacridine amyl gel. The reversing change of oligomeric form of protein with molecule size 2 Mda in polymeric form 28 Mda under impact of guanidinhydrochloride. Under urolithiasis, the form of protein associated with non-organic components and with size of macromolecular complex larger than 1500 nm was detected. The diagnostic criterion of urolithiasis was proposed based on totality of biochemical and biophysical analyses of urine.

[Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents].

Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. While being of a relatively low genetic capacity, the virus can be ranked as a standard for pathogenicity with the ability to evade the host immune response in uttermost perfection. The EHF virus has similarities with retroviruses, but belongs to (-)RNA viruses of a nonretroviral origin. Genetic elements of the virus, NIRV, were detected in animal and human genomes. EHF virus glycoprotein (GP) is a class I fusion protein and shows more similarities than distinctions in tertiary structure with SIV and HIV gp41 proteins and even influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying the molecular basis of its pathogenesis may contribute to new findings in therapy of severe conditions leading to a fatal outcome.

[Diagnostic errors when referring patients for cataract surgery].

AIM: To study the frequency of patients with macular pathology being wrongly diagnosed with cataract and possible reasons for this to occur. MATERIAL AND METHODS: A total of 1390 patients (1390 eyes), in whom cataract turned out to be not the main cause of visual impairment, were recruited as research subjects. To reveal the reasons for misdiagnosis, we resorted to methods of ophthalmic examination that are available at ambulatory care facilities, i.e. visual acuity measurement, slit lamp biomicroscopy of the anterior and posterior eye segments, direct and indirect ophthalmoscopy. RESULTS: In most patients (72.6%) visual acuity was decreased due to macular pathology, especially age-related macular degeneration (AMD)--736 eyes (72.9%). Less common were degenerative myopia (10%), idiopathic macular hole (8.4%), epiretinal macular fibrosis (5.1%), and secondary macular changes of vascular, traumatic, or inflammatory genesis (3.6%). In 76.6% of eyes with macular pathology ophthalmoscopy was perfectly feasible and could be performed by a local ophthalmologist. Only in 23.4% of cases there was a dense posterior capsule opacification or nuclear cataract that impeded visualization of macular structures. CONCLUSIONS: The main reason for misdiagnosis of macular pathology and referring the patient to cataract surgeon was the neglect of apparent discordance between visual acuity and lens transparency. One should aim at adequate assessment of macular zone by all means, including non-contact ophthalmoscopy with 60 or 90 D aspherical lenses or Hruby lens and red-free examination.

Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents.

Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. While being of a relatively low genetic capacity, the virus can be ranked as a standard for pathogenicity with the ability to evade the host immune response in uttermost perfection. The EHF virus has similarities with retroviruses, but belongs to (-)RNA viruses of a nonretroviral origin. Genetic elements of the virus, NIRV, were detected in animal and human genomes. EHF virus glycoprotein (GP) is a class I fusion protein and shows more similarities than distinctions in tertiary structure with SIV and HIV gp41 proteins and even influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying the molecular basis of its pathogenesis may contribute to new findings in therapy of severe conditions leading to a fatal outcome.

Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments.

This study is devoted to the antiviral activity of peptide fragments from the PB1 protein - a component of the influenza A RNA polymerase. The antiviral activity of the peptides synthesized was studied in MDCK cell cultures against the pandemic influenza strain A/California/07/2009 (H1N1) pdm09. We found that peptide fragments 6-13, 6-14, 26-30, 395-400, and 531-540 of the PB1 protein were capable of suppressing viral replication in cell culture. Terminal modifications i.e. N-acetylation and C-amidation increased the antiviral properties of the peptides significantly. Peptide PB1 (6-14) with both termini modified showed maximum antiviral activity, its inhibitory activity manifesting itself during the early stages of viral replication. It was also shown that the fluorescent-labeled analog of this peptide was able to penetrate into the cell. The broad range of virus-inhibiting activity of PB1 (6-14) peptide was confirmed using a panel of influenza A viruses of H1, H3 and H5 subtypes including those resistant to oseltamivir, the leading drug in anti-influenza therapy. Thus, short peptide fragments of the PB1 protein could serve as leads for future development of influenza prevention and/or treatment agents.

Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins.

Influenza A virus is one of the major human pathogens. Despite numerous efforts to produce absolutely effective anti-influenza drugs or vaccines, no such agent has been developed yet. One of the main reasons for this complication is the high mutation rate and the specific structure of influenza A viruses genome. For more than 25 years since the first mapping of the viral genome, it was believed that its 8 genome segments encode 10 proteins. However, the proteome of influenza A viruses has turned out to be much more complex than previously thought. In 2001, the first accessory protein, PB1-F2, translated from the alternative open reading frame, was discovered. Subsequently, six more proteins, PB1-N40, PA-X, PA-N155, PA-N182, M42, and NS3, have been found. It is important to pay close attention to these novel proteins in order to evaluate their role in the pathogenesis of influenza, especially in the case of outbreaks of human infections with new avian viruses, such as H5N1 or H7N9. In this review we summarize the data on the molecular mechanisms used by influenza A viruses to expand their proteome and on the possible functions of the recently discovered viral proteins.