Vol 62, No 4 (2017)
- Year: 2017
- Published: 20.08.2017
- Articles: 7
- URL: https://virusjour.crie.ru/jour/issue/view/18
- DOI: https://doi.org/10.36233/0507-4088-2017-62-4
Full Issue
REVIEWS
LUJO HEMORRHAGIC FEVER
Abstract
Lujo hemorrhagic fever (LHF) is a viral disease accompanied with fever, headache, vomiting, diarrhea, arthralgia, myalgia and numerous signs of hemorrhagic syndrome. LHF causes a clinical syndrome remarkably similar to Lassa hemorrhagic fever. The first case of LHF occurred in Johannesburg, South Africa, in 2008. There was a secondary transmission from the index patient to four healthcare workers. Four of the five patients died. The etiologic agent of LHF is Lujo virus (LUJV) belonging to Arenavirus genus of the Arenaviridae Family. Virus Lujo is the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa during the last 40 years. Data about epidemiology, clinical characteristics and diagnostics of LHF, properties of Lujo virus (according to phylogenetic analysis), and recommended precautions for preventing secondary transmission are considered in this paper.
Problems of Virology. 2017;62(4):149-153
149-153
ORIGINAL RESEARCH
MOLECULAR EPIDEMIOLOGICAL ANALYSIS OF HIV INFECTION IN NORTHERN SEAPORTS OF RUSSIA
Abstract
The results of the molecular-epidemiological analysis of HIV-1 variants circulating in Arkhangelsk and Murmansk - northern seaports of Russia - were presented. In these seaports the HIV-1 variants belonging to subtype A1 were predominant (93% in Murmansk, 83% in Arkhangelsk). In addition to these variants, viruses of other subtypes such as B, C, D and recombinant forms CRF02_AG and CRF03_AB were identified. The heterogeneity of circulating HIV-1 variants was higher in Arkhangelsk than in Murmansk. According to the results of phylogenetic analysis, subtype A1 sequences formed the common branch with nucleotide sequences of IDU-A strains found in other regions of Russia. HIV-1 variants of subtype B sub-clustered with sequences of East European B-variants. The recombinant strains CRF02_AG formed the common branch with HIV-1 sequences from Central Asia republics of the former USSR. Among 124 therapy-naive patients from Arkhangelsk and Murmansk (n = 124) the transmitted resistance was less than 5%.
Problems of Virology. 2017;62(4):154-161
154-161
DIMERIC BISBENZIMIDAZOLES SUPPRESS THE HERPES SIMPLEX VIRUS AND HUMAN CYTOMEGALOVIRUS INFECTIONS IN CELL СULTURES
Abstract
Antiviral activity of new AТ-specific fluorescent symmetric dimeric bisbenzimidazoles of DBА(n) series was assessed in the cell models of infections caused by type 1 herpes simplex virus (HSV1) and human cytomegalovirus (CMV). In DBA(n) molecules bisbenzimidazole fragments are bound to an oligomethylene liner with varied number of methylene groups in the linker (n = 1, 3, 5, 7, 9, 11). In contrast to DB(n) dimeric bisbenzimidazoles, in DBA(n) series terminal fragments of macromolecules contain N-dimethylaminopropylcarboxamide groups instead of N-methylpiperazine groups. DBА(n) compounds better dissolve in water, pass across plasma and nuclear membrane, and stain DNA in living cells. DBA(1) and DBA(7) produced therapeutic effects in HSV1 infection; DBA(7) completely suppressed the infection. DBA(11) displayed in vitro therapeutic activity in HSV1 and CMV infections. In addition, DBA(7) and DBA(1) showed microbicidal activity. Thus, DBA(11), which is active against two viruses causing severe diseases with serious health consequences for immunodeficient individuals, should be further investigated. High antiviral activity of DBA(7) in all test models indicates that this compound is a promising active agent for innovative antiviral drugs.
Problems of Virology. 2017;62(4):162-168
162-168
ANTIVIRAL ACTIVITY OF PHOSPRENYL AND GAMAPREN AGAINST INFECTION CAUSED BY INFLUENZA A (H5N1) VIRUS IN CELL CULTURE
Abstract
The antiviral activity of Phosprenyl and Gamapren in vitro against highly pathogenic strain of avian influenza H5N1 virus was studied. Inoculation of the virus to the susceptible cell culture led to development of the cytopathogenic effect. Preliminary introduction of Phosprenyl and Gamapren an hour prior to infecting the cells with virus 10.0 TCID50 dose completely inhibited the cytopathogenic activity of the virus. At higher doses of virus (100.0 TCID50) significant inhibition of the infectious activity of the virus was observed: 70% of infected cells survived under the action of Phosprenyl, and 90% under the action of Gamapren. With the introduction of the preparations simultaneously with the infection of cells with virus at a dose of 10.0 TCID50 virtually 100% of infected cells survived, while in control cultures death of 100% of the cells occurred. After infection with the virus at a dose of 100.0 TCID50 Phosprenyl and Gamapren caused 50% protection of the cells. The antiviral effect of the drugs Phosprenyl and Gamapren may be associated not only with their virulicidal, but with anti-viral activity as well.
Problems of Virology. 2017;62(4):168-173
168-173
CYTOPENIAS AND THEIR CORRECTION DURING ANTIVIRAL THERAPY OF CHRONIC HEPATITIS C IN PATIENTS WITH GENOTYPE 1
Abstract
The main reason for the ineffectiveness of antiviral therapy in patients with chronic hepatitis C that impedes full and adequate treatment of IFN-α and ribavirin is the development of neutropenia and thrombocytopenia. The present study included 63 patients (59% men and 41% women) with chronic hepatitis C that did not previously receive antiviral therapy. All patients had HCV genotype-1 (15 patients with genotype 1a; 42 people, with genotype 1b; 6 patients, with genotypes (1a + 1b)). The patients’ age was 33.8 ± 0.7 years, with term of infection 6,1 ± 0,8 years. It was shown that in the case of treatment with Peg-IFN-alpha in combination with ribavirin, a significant decrease in the number of white blood cells, neutrophils and platelets prevailed in patients with HCV-monoinfected genotype 1b in the F0-F2 stages (2,8-8,6 kPa) at METAVIR. With the development of moderate “early” (less than 12 weeks of antiviral therapy) and for the prevention of “late” (more than 12 weeks of treatment) neutropenia, appointment of immune medicine likopid (glucosaminylmuramyldipeptide) at a dosage of 1 mg, 2 times a day for 20 days, in patients with chronic hepatitis C (genotype 1b ) with
Problems of Virology. 2017;62(4):174-178
174-178
A COMPARATIVE CHARACTERISTIC OF ANTIGENIC PROPERTIES OF RECOMBINANT AND NATIVE HBS-ANTIGENS WITH G145R MUTATION AND EVALUATION OF THEIR IMMUNOGENICITY
Abstract
Background: One of the important reasons for spreading of hepatitis B virus (HBV) under conditions of vaccine pressure is emergence of escape mutations. Prevalent G145R mutation in S-gene leads to the most expressed changes of serological properties of HBV. Consequently, HBsAg is modified so thoroughly that it cannot be recognized by the majority of anti-HBs. Mutant G145R also differs from a wild type HBsAg by its immunogenic properties. At present, the relevance of enhancement of hepatitis B vaccine in view of mutant virus variants has been recognized. Objectives: a comparative study of antigenic and immunogenic properties of native and recombinant G145R mutants and an estimation of possibility for developing antigenic component of hepatitis B vaccine with G145R mutation in HBsAg. Methods: antigenic properties of recombinant HBsAg with G145R mutation were compared with each other and with native mutants by serological fingerprinting method. Then, BALB/c mice and sheep were immunized with selected recombinant antigen under different protocols. Titers of antibodies specific to wild type or mutant G145R type of HBsAg in sera of immunized animals were measured. Results: it was found that not all the recombinant HBsAg variants with G145R substitution have the same antigenic properties as native HBsAg with similar mutation. Recombinant HBsAg selected according to the principle of antigenic similarity possesses immunogenicity in mice and sheep causing the production of antibodies reacting with native wild and mutant type HBsAg. It was shown that mutant antigen is less immunogenic, requires larger doses and more time for the development of immune response; however, it is capable of causing an antibody level comparable with wild type antigen. Conclusion: preliminary selection of recombinant HBsAg containing G145R mutation with antigenic and immunogenic properties similar to the native analogue creates the basis for development of a specific component of hepatitis B vaccine with escape mutation G145R in HBsAg.
Problems of Virology. 2017;62(4):179-186
179-186
CYTOKINES AND ANTIBODIES IN EXPERIMENTAL INFECTION OF WILD AND LABORATORY RODENTS (RODENTIA) WITH TICK-BORNE ENCEPHALITIS VIRUS
Abstract
Persistence modeling was performed by means of infection of the wild rodents: northern red-backed vole Myodes rutilus (Pallas, 1779) and striped field mouse Apodemus agrarius (Pallas, 1771), as well as of laboratory mice with the tick-borne encephalitis virus (TBEV) in tick suspensions with subsequent detection of the TBEV, hemagglutination inhibition and virus-neutralizing antibodies, as well as expression of cytokine genes during 4 months. Detection rate of the TBEV RNA and antigen E remained high during the whole period of observations; however, virus pathogenic for laboratory suckling mice was isolated mainly during a period of 8 days post infection. At the late stages of the persistent infection (1-4 months) the TBEV RNA detection rate in northern red-backed voles and laboratory mice remained high, whereas in striped field mice it significantly declined (p < 0.001). The viral loads were significantly higher (p < 0.001) in the wild rodents compared to the laboratory mice. Average frequencies of Th2 cytokine gene expression were similar for M. rutilus (50.0 ± 8.5%) and A. agrarius (50.0 ± 9.6%) during the whole period, but Th1 cytokine mRNA detection rate after transcription activation in 2 days post infection and subsequent return to the original values were different (22.2 ± 5.0% and 38.1 ± 7.6%, respectively (p > 0.05)). Meanwhile, a part of animals with interleukin 1β mRNA was significantly higher among A. agrarius than among M. rutilus (p < 0.05), which might cause low levels of spontaneous TBEV infection of field mice compared to red voles. Hemagglutination inhibition and virus-neutralizing antibodies were revealed in wild rodents in 30 days post infection and remained at detectable levels during 4 months. Thus, the TBEV persistence in small rodents was accompanied by the detection of the pathogenic virus in the early period, the viral RNA and antigen E during 4 months with high viral loads in wild animals exceeding the values in laboratory mice. Changes in the proinflammatory cytokine gene expression frequencies and the TBEV-specific antibodies pointed at immunomodulation as the possible mechanism of the TBEV persistence.
Problems of Virology. 2017;62(4):186-192
186-192