Репозиторий Университета

© 2019 Elsevier B.V. Lassa fever is a severe viral hemorrhagic illness caused by Lassa virus. Based on estimates, the number of LASV infections ranges from 300,000 to 500,000 cases in endemic areas with a fatality rate of 1%. Development of fast and sensitive tools for the control and prevention of Lassa virus infection as well as for clinical diagnostics of Lassa fever are crucial. Here we reported development and evaluation of a one-step quantitative RT-qPCR assay for the Lassa virus detection – LASV-Fl. This assay is suitable for the detection of lineages I-IV of Lassa virus. The limit of detection of the assay ranged from 103 copies/ml to 105 copies/ml and has 96.4% diagnostic sensitivity, whereas analytical and diagnostic specificities both were 100%. Serum, whole blood and tissue are suitable for use with the assay. The assay contains all the necessary components to perform the analysis, including an armored positive control (ARC+) and an armored internal control (IC). The study was done during the mission of specialized anti-epidemic team of the Russian Federation (SAET) in the Republic of Guinea in 2015-2018. Based on sequencing data, LASV-specific assay was developed using synthetic MS2-phage-based armored RNA particles, RNA from Lassa virus strain Josiah, and further, evaluated in field conditions using samples from patients and Mastomys natalensis rodents.

© 2019 National Academy of Sciences. All rights reserved. Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those observed in HBeAg-negative human HBV. Deep sequencing and in situ hybridization suggest that HBeAg-negative shrew HBVs cause intense hepatotropic monoinfections and low within-host genomic heterogeneity. Geographical clustering and low MSHBV/CSHBV-specific seroprevalence suggest focal transmission and high virulence of shrew HBVs. HBeAg negativity is thus an ancient HBV infection pattern, whereas Ntcp usage for entry is not evolutionarily conserved. Shrew infection models relying on CSHBV/MSHBV revertants and human HBV will allow comparative assessments of HBeAg-mediated HBV pathogenesis, entry, and species barriers.

© 2018, MDPI AG. All rights reserved. Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come.

© 2018 Grybchuk et al. In this work, we analyzed viral prevalence in trypanosomatid parasites (Blechomonas spp.) infecting Siphonaptera and discovered nine species of viruses from three different groups (leishbunyaviruses, narnaviruses, and leishmaniaviruses). Most of the flagellate isolates bore two or three viral types (mixed infections). Although no new viral groups were documented in Blechomonas spp., our findings are important for the comprehension of viral evolution. The discovery of bunyaviruses in blechomonads was anticipated, since these viruses have envelopes facilitating their interspecific transmission and have already been found in various trypanosomatids and metatranscriptomes with trypanosomatid signatures. In this work, we also provided evidence that even representatives of the family Narnaviridae are capable of host switching and evidently have accomplished switches multiple times in the course of their evolution. The most unexpected finding was the presence of leishmaniaviruses, a group previously solely confined to the human pathogens Leishmania spp. From phylogenetic inferences and analyses of the life cycles of Leishmania and Blechomonas, we concluded that a common ancestor of leishmaniaviruses most likely infected Leishmania first and was acquired by Blechomonas by horizontal transfer. Our findings demonstrate that evolution of leishmaniaviruses is more complex than previously thought and includes occasional host switching. IMPORTANCE Flagellates belonging to the genus Leishmania are important human parasites. Some strains of different Leishmania species harbor viruses (leishmaniavi-ruses), which facilitate metastatic spread of the parasites, thus aggravating the disease. Up until now, these viruses were known to be hosted only by Leishmania. Here, we analyzed viral distribution in Blechomonas, a related group of flagellates parasitizing fleas, and revealed that they also bear leishmaniaviruses. Our findings shed light on the entangled evolution of these viruses. In addition, we documented that Blechomonas can be also infected by leishbunyaviruses and narnaviruses, viral groups known from other insects’ flagellates.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. As revealed by the recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America, YFV control measures need urgent rethinking. Over the last decade, most reported outbreaks occurred in, or eventually reached, areas with low vaccination coverage but that are suitable for virus transmission, with an unprecedented risk of expansion to densely populated territories in Africa, South America and Asia. As reflected in the World Health Organization’s initiative launched in 2017, it is high time to strengthen epidemiological surveillance to monitor accurately viral dissemination, and redefine vaccination recommendation areas. Vector-control and immunisation measures need to be adapted and vaccine manufacturing must be reconciled with an increasing demand. We will have to face more yellow fever (YF) cases in the upcoming years. Hence, improving disease management through the development of efficient treatments will prove most beneficial. Undoubtedly, these developments will require in-depth descriptions of YFV biology at molecular, physiological and ecological levels. This second section of a two-part review describes the current state of knowledge and gaps regarding the molecular biology of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

© 2018, Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. Enteric viruses are the most common cause of acute gastroenteritis (AGE) in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus (RVA) infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RVA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCR-genotyping. The main causes for hospitalization of children with AGE were RVA (40.1%), followed by noroviruses (11.4%), while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants (G6 and P[9]) highlights the need to conduct continuous epidemiological monitoring of RVA infection.

© 2018 Elsevier Masson SAS A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1–4-alkyl-1,2,3-triazol-1,4-diyl groups at 3′-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC50 ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11.

© 2018 American Society for Microbiology.  The discovery of highly diverse nonprimate hepatoviruses illuminated the evolutionary origins of hepatitis A virus (HAV) ancestors in mammals other than primates. Marsupials are ancient mammals that diverged from other Eutheria during the Jurassic. Viruses from marsupials may thus provide important insight into virus evolution. To investigate Hepatovirus macroevolutionary patterns, we sampled 112 opossums in northeastern Brazil. A novel marsupial HAV (MHAV) in the Brazilian common opossum (Didelphis aurita) was detected by nested reverse transcription- PCR (RT-PCR). MHAV concentration in the liver was high, at 2.5 × 10 9 RNA copies/g, and at least 300-fold higher than those in other solid organs, suggesting hepatotropism. Hepatovirus seroprevalence in D. aurita was 26.6% as determined using an enzyme-linked immunosorbent assay (ELISA). Endpoint titers in confirmatory immunofluorescence assays were high, and marsupial antibodies colocalized with anti- HAV control sera, suggesting specificity of serological detection and considerable antigenic relatedness between HAV and MHAV. MHAV showed all genomic hallmarks defining hepatoviruses, including late-domain motifs likely involved in quasienvelope acquisition, a predicted C-terminal pX extension of VP1, strong avoidance of CpG dinucleotides, and a type 3 internal ribosomal entry site. Translated polyprotein gene sequence distances of at least 23.7% from other hepatoviruses suggested that MHAV represents a novel Hepatovirus species. Conserved predicted cleavage sites suggested similarities in polyprotein processing between HAV and MHAV. MHAV was nested within rodent hepatoviruses in phylogenetic reconstructions, suggesting an ancestral hepatovirus host switch from rodents into marsupials. Cophylogenetic reconciliations of host and hepatovirus phylogenies confirmed that hostindependent macroevolutionary patterns shaped the phylogenetic relationships of extant hepatoviruses. Although marsupials are synanthropic and consumed as wild game in Brazil, HAV community protective immunity may limit the zoonotic potential of MHAV.

© 2018 American Society for Microbiology. All Rights Reserved. Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

© 2018 Deutsche Pharmazeutische Gesellschaft Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, is the leading cause of arboviral neuroinfections in Europe. Only a few classes of the nucleoside and non-nucleoside inhibitors were investigated against TBEV reproduction. Paving the way to previously unexplored areas of anti-TBEV chemical space, we assessed the inhibition of TBEV reproduction in the plaque reduction assay by various compounds derived from cyanothioacetamide and cyanoselenoacetamide. Compounds from seven classes, including 4-(alkylthio)-2-aryl-3-azaspiro[5.5]undec-4-ene-1,1,5-tricarbonitriles, 3-arylamino-2-(selenazol-2-yl)acrylonitriles, ethyl 6-(alkylseleno)-5-cyano-2-oxo-1,2-dihydropyridine-3-carboxylates, 6-(alkylseleno)-2-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles, 2-(alkylseleno)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles, 8-selenoxo-3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene-1,9-dicarbonitriles, and selenolo[2,3-b]quinolines, inhibited TBEV reproduction with EC50 values in the micromolar range while showing moderate cytotoxicity and no inhibition of enterovirus reproduction. Thus, new scaffolds with promising anti-TBEV activity were found.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland.  Wild ducks are known to be able to carry avian influenza viruses over long distances and infect domestic ducks, which in their turn infect domestic chickens. Therefore, prevention of virus transmission between ducks and chickens is important to control the spread of avian influenza. Here we used a low pathogenic wild aquatic bird virus A/duck/Moscow/4182/2010 (H5N3) for prevention of highly pathogenic avian influenza virus (HPAIV) transmission between ducks and chickens. We first confirmed that the ducks orally infected with H5N1 HPAIV A/chicken/Kurgan/3/2005 excreted the virus in feces. All chickens that were in contact with the infected ducks became sick, excreted the virus, and died. However, the ducks orally inoculated with 10 4 50% tissue culture infective doses of A/duck/Moscow/4182/2010 and challenged 14 to 90 days later with H5N1 HPAIV did not excrete the challenge virus. All contact chickens survived and did not excrete the virus. Our results suggest that low pathogenic virus of wild aquatic birds can be used for prevention of transmission of H5N1 viruses between ducks and chickens.

© 2018 Elsevier B.V. Background: Very recently, a novel European hantavirus, Sochi virus, has been discovered which causes severe courses of hantavirus disease with a case fatality rate of about 15 percent. Objectives: We aimed to study to which extent and with which clinical severity children were affected by Sochi virus infection. Study design: Sochi virus infection of patients was confirmed by molecular, serological, and epizoonotic studies. Clinical and laboratory parameters were analyzed for the age group of up to 15 years (n = 6) in comparison to all older patients (n = 56). Results: 9.7 percent of patients with hantavirus disease studied (6/62) were up to 15 years old. The children showed moderate to severe clinical courses similarly to the situation in adults. Conclusions: While children are in general considered to be less affected by hantavirus infections than adults, in case of highly pathogenic hantaviruses, such as Sochi virus, frequency of clinical cases as well as their clinical course are comparable between children and adults. Therefore, hantavirus disease, particularly in regions endemic to highly pathogenic hantaviruses, should be considered in cases of unclear fever and kidney/pulmonary failure in children.

© 2017 Elsevier B.V. KISS1 tumor suppressor protein regulates cancer cell invasion via MMP9 metalloproteinase. Downregulation of KISS1 gene expression promotes progression of breast cancer and melanoma, resulting in the development of distant metastases. In the current study, we investigated whether restoration of KISS1 expression in KISS1-deficient human metastatic breast cancer cells holds potential as an advanced anticancer strategy. To this end we engineered an infectivity-enhanced conditionally-replicative human adenovirus type 5 encoding KISS1 as an “arming” transgene in the Ad5 E3 region for an ectopic KISS1 expression in transduced cancer cells. The oncolytic potential of the vector was examined using brain-invading metastatic clones of CN34 and MDA-MB-231 breast cancer cells, which supported high levels of AdKISS1 replication, correlating with a robust CRAd-mediated cytotoxicity. Secretion of cellular factors responsible for tumor angiogenesis, cell-to-cell communication and anti-tumoral immune responses upon KISS1 expression in breast cancer cells was analyzed by a RayBiotech Kiloplex Quantibody array. Overall, our results indicate that KISS1 transgene expression provides an important benefit for CRAd-mediated cytotoxicity in breast cancer cells and holds potential as an anticancer treatment in conjunction with oncolytic virotherapy of breast and other metastatic cancers.

© 2018 Wiley-VCH Verlag GmbH  &  Co. KGaA, Weinheim The rational design of broad-spectrum antivirals requires data on antiviral activity of compounds against multiple viruses, which are often not available. We have developed a panel of (+)ssRNA viruses composed of Enterovirus and Flavivirus genera members allowing to study these activity spectra. Antiviral activity profiling of a set of nucleoside analogues revealed N4-hydroxycytidine as an efficient inhibitor of replication of coxsackieviruses and other enteroviruses, but ineffective against tick-borne encephalitis virus. Furano[2, 3-d]pyrimidine nucleosides with n-pentyl or n-hexyl tails showed selective inhibition of Enterovirus A representatives. 5-(Tetradec-1-yn-1-yl)-uridine showed selective inhibition of tick-borne encephalitis virus at the micromolar level.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study the effectiveness of two-step treatment of female patients with cervical intraepithelial neoplasia (CIN) associated with papillomavirus infection (PVI). Patients and methods. 126 female patients of reproductive age were examined (mean age – 31.4 ± 2.1 years), in whom CIN was associated with papillomavirus infection (PVI). In all cases, cervical pathologies – low-grade squamous intraepithelial lesions (L-SIL) have been found. In all patients treatment included a surgical step (laser and plasma energy) and medication, which was employed in 101 (80.1%) patients (treatment group). 25 (19.9%) women comprised the control group, since they did not receive post-operative pathogenetic therapy. In the treatment group, patients received an immunostimulating and antiviral drug inosine pranobex (IP) – Isoprinosine. Results. The effectiveness of treatment was assessed after 60 and 120 days from the termination of complex therapy (treatment group), or surgical intervention (control group). After a 60-day period, complete elimination of virus was noted 97 (96%) patients of the treatment group and in 18 (72%) of the control group. After 120 days, PVI relapse was recorded in 3 women of the treatment group (3%) and in 4 (22%) – of the control group among patients with complete elimination of virus. Conclusion. The use of IP as monotherapy is an optimal solution ensuring minimal risks of relapses of pathological PVI. Preparations of pure IFN and their inductors do not always promote complete elimination of PVI owing to interferon resistance of HPV-infected patients.

Research objective was assessment of a possibility of primary diagnosis of viruses Epstein-Burr, a cytomegalovirus, a virus of herpes of the 6th type in oral liquid and also influences of herpes infection on development and the clinical course of precancer diseases of the oral mucosa and the red border of lips (RBL). Profound clinic-immunological examination is conducted to 60 patients: the first group are have made 20 patients with an erosive and ulcer form of the lichen planus, the second - 20 people with an erosive form of a leukoplakia, a third - 20 people without diseases of the oral mucosa. As a result of work detection herpes infection is revealed high (90%). The combined infection with a virus Epstein-Burr and a virus of herpes of the 6th type was observed more than at a half of patients. The imbalance of factors of local immunity of the oral cavity in the form of increase in the IgG profile, decrease in concentration of IGA, lysozyme, and increase in an indicator of Ksb three times in comparison with norm and also substantial increase of level of pro-inflammatory cytokin IL 1β and FNO-α is found in patients with precancer diseases of the oral mucosa. Characteristic clinical feature of the precancer diseases associated with latent herpes infection is the long, recidivous current, persistent to traditional therapy. The research of oral liquid and blood on herpes viruses and consultation of the infectiologist is recommended to all patients with precancer diseases.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To offer a clinical and laboratory characteristic of coronavirus infection in hospitalised children. Patients and methods. The group of study included 50 children, who were diagnosed with coronavirus infection by polymerase chain reaction (PCR). Mono-coronavirus infection was found in 40 children (80%), mixed virus infection conditioned by a combination of two or three viruses - in 10 children (20%). Results. In all examined children with coronavirus infection disease had an acute onset and took a mild or moderate course. In general, the clinical picture of disease was manifested by cough, signs of rhinitis (stuffy nose, mucus discharge from the nose), febrile fever (in 52.5% of patients with mono-infection and in 80% of children with mixed infection), laryngotracheitis with laryngeal stenosis grade 1 (in 52.5% with mono-infection and in 80% with mixed infection). In 10% of children with monoinfection and in 50% of children with mixed infection gastrointestinal dysfunction was noted in the form of repeated vomiting to 2-6 times, diarrhoea to 1-4 times daily without pathological admixtures. Haematological parameters did not show any characteristic specificities in any child in both mono-infection and mixed infection. Cclusionon. Catarrhal inflammation is the leading clinical syndrome in mono- and mixed coronavirus infection; disease was manifested by cough, often - elevated body temperature, signs of stenosing laryngitis; part of children developed gastrointestinal dysfunction.

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reservbed. The creation in the middle of the 20th century vaccines against poliomyelitis (PM) - inactivated vaccine (IPV) and live oral vaccine from Sabin strains (OPV) with various properties, advantages and disadvantages, but highly effective, made it possible to implement the idea of elimination of PM. Since 1988, the WHO Global Program of PM eradication has achieved remarkable success: the incidence of PM caused by wild poliovirus (PV) has been reduced by 10 thousand times, the number of endemic countries has been reduced to 3, the circulation of wild PV has been discontinued in 4 regions of the world the wild type 2 of PV has been eradicated, and wild type 3 of PV has not been detected for almost 5 years. Under conditions of a decrease in the incidence of PM caused by wild PV, the known negative properties of trivalent OPV made its further use problematic. These negative properties are: 1) the ability to cause post-vaccination complications and 2) the genetic instability of Sabin strains, especially PV of type 2, and their ability under certain conditions (primarily in conditions of low collective immunity to PV) to quickly restore neurovirulence, transforming into circulating vaccine-derived PV (VDPV), capable of causing incidents and outbreaks of PM. In order to reduce the risk associated primarily with type 2 PV, WHO proposed a global switch to the use of bivalent OPV from types 1 and 3, completed in 2016. In 2019, WHO plans to complete eradication of type 1 and 3 PVs, and in 2022 completely abandon the OPV. The precondition for the safety of such tactics is the maintenance of high collective immunity to PM. There are several threats to the security of this strategy. PVs can "silently" circulate in the human population for a long time without clinical manifestations of PM, which, with inadequate epidemiological surveillance can lead to the return of PM. The reintroduction of both wild PV and Sabin strains can occur from institutions that preserve / work with PV. The source of VDPV can be people with primary immunodeficiencies, which continuously excrete PV. It is necessary to maintain surveillance over the PM, expand additional types of surveillance for the PV, strict containment of all PVs. The only way to maintain collective immunity is immunization with trivalent IPV. The current global shortage of IPV poses a significant threat to the world's epidemiological well-being. The solution to the problem is the development of a new generation of safe and effective vaccines, improving the ways of introducing IPV, developing antiviral drugs.

© 2018 Dynasty Publishing House. All rights reserved. The objective: To optimize a tactics of examination and treatment of patients with a benign cervical pathology associated with papillomavirus infection (PVI) in female patients of reproductive age. Patients and methods: 124 patients aged 22 to 35 years underwent complex examination and treatment. Two groups were singled out: the first (main) group included 72 patients, who in the postoperative period received treatment with an antiviral immunostimulating drug isoprinosine, the second group comprised 52 patients, who did not receive the antiviral medication (control group). Inosine pranobex (isoprinosine) was administered 3 g/day (2 tablets 3 times daily) for 28 days. A carbon dioxide (CO2) laser and argon plasma were used to destroy the affected uterine cervical epithelium. Results: The Pap test found various pathological changes in 112 (90.3%) patients. ASCUS smear results had similar incidence rates in the groups 16 and 18% (p > 0.05). The incidence of LSIL in the groups was 31.9 and 32.6%, respectively (p > 0.05). In the basic group, 60 days afterwards complete elimination of virus was noted in 95.8% of cases; in the control group in 78.8%. The frequency of HPV infection recurrence among patients with complete virus elimination was 2.9% in the basic group, in the control group - 14.6%. Conclusion: The employment of the surgical stage permits to destroy pathological tissue, deactivate virus at the local level and prepare conditions for deactivation of virus in the body. Postoperative antiviral and immunostimulating therapy not only ensures practically complete elimination of virus but also reduces recurrences of PVI.