After infection with the neurotropic CAM/RBH measles virus (MV) strain, newborn Lewis rats succumb to an acute necrotizing encephalopathy. Passive transfer of neutralizing monoclonal antibodies directed against MV hemagglutinin prevented this disease process. Instead, either an antibody-induced acute or subacute measles encephalitis developed after a prolonged incubation period with a restricted expression of MV structural proteins. The molecular biological analysis of MV gene expression in brain tissue of rats treated with MV-neutralizing antibodies revealed a transcriptional restriction of viral mRNAs, particularly for the envelope proteins, leading to a steep expression gradient. Based on in situ hybridization, it was concluded that the efficiency of transcription of viral genes at the single-cell level is reduced compared with that of controls. Passive immunization with monoclonal antibodies directed against other MV structural proteins proved to be ineffective. Similar results were obtained in MV-infected weanling Brown Norway rats. These rats developed a clinically silent encephalitis in the presence of high titers of neutralizing antibodies. In such animals, a pronounced attenuation of the viral gene transcription was observed. These findings indicated that neutralizing antibodies directed against a restricted set of specific antigenic sites on the viral hemagglutinin protein expressed on cell membranes exert a modulating effect on the viral gene expression at the level of transcription. This phenomenon contributes to the switch from the acute cytopathic effect to a persistent infection in the central nervous system.
Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8+ T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8+ T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1Bal) and beta-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8+ T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8+ T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.
Investigation of influenza A (H3N2) epidemic of 1983 in Leningrad revealed simultaneous circulation of 3 antigenic variants similar to A/Bangkok/1/79, A/Bangkok/2/79, and A/Philippines/2/82 with significant predominance of the first antigenic variant. The viruses related to A/Philippines/2/82 comprising one-third of all isolations produced antibodies of a wide spectrum unlike the other two variants whose antisera neutralize actively the homologous virus only. The possibility of selecting epidemic strains of the A/Philippines/2/82 variety as vaccine strain candidates is discussed.
Viral strains from the foci of tick-borne encephalitis in Western Siberia and the Far East, producing the disease which takes the clinical course of different severity, have been shown to possess similar biological properties. A high mortality rate in the foci of tick-borne encephalitis in the Primorye Territory is the consequence of the weak latent immunization of the population, which is due, in its turn, to some specific features of the epizootic process in this area.
Department of Marine Microbiology and Biogeochemistry, NIOZ Royal Netherlands Institute for Sea Research, and University of Utrecht, P.O. Box 59, 1790 AB Den Burg, Texel, The Netherlands. email@example.com.
Global climate change-induced warming of the Artic seas is predicted to shift the phytoplankton community towards dominance of smaller-sized species due to global warming. Yet, little is known about their viral mortality agents despite the ecological importance of viruses regulating phytoplankton host dynamics and diversity. Here we report the isolation and basic characterization of four prasinoviruses infectious to the common Arctic picophytoplankter Micromonas. We furthermore assessed how temperature influenced viral infectivity and production. Phylogenetic analysis indicated that the putative double-stranded DNA (dsDNA) Micromonas polaris viruses (MpoVs) are prasinoviruses (Phycodnaviridae) of approximately 120 nm in particle size. One MpoV showed intrinsic differences to the other three viruses, i.e., larger genome size (205 ± 2 vs. 191 ± 3 Kb), broader host range, and longer latent period (39 vs. 18 h). Temperature increase shortened the latent periods (up to 50%), increased the burst size (up to 40%), and affected viral infectivity. However, the variability in response to temperature was high for the different viruses and host strains assessed, likely affecting the Arctic picoeukaryote community structure both in the short term (seasonal cycles) and long term (global warming).
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Cites: Mol Syst Biol. 2011 Oct 11;7:539 PMID 21988835
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Cites: ISME J. 2014 Oct;8(10):1953-61 PMID 24553471
The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. Molecular evolutionary analyses of the 2009 pandemic influenza A H1N1 [A(H1N1)pdm09] virus revealed two major clusters, cluster I and cluster II. Although the pathogenicity of viruses belonging to cluster I, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster II, which has spread more widely in the world, has not been studied in this animal model. Here, we characterized two Norwegian isolates belonging to cluster II, namely, A/Norway/3568/2009 (Norway3568) and A/Norway/3487-2/2009 (Norway3487), which caused distinct clinical symptoms, despite their genetic similarity. We observed more efficient replication in cultured cells and delayed virus clearance from ferret respiratory organs for Norway3487 virus, which was isolated from a severe case, compared with the efficiency of replication and time of clearance of Norway3568 virus, which was isolated from a mild case. Moreover, Norway3487 virus to some extent caused more severe lung damage in nonhuman primates than did Norway3568 virus. Our data suggest that the distinct replicative and pathogenic potentials of these two viruses may result from differences in their biological properties (e.g., the receptor-binding specificity of hemagglutinin and viral polymerase activity).
A strain of Tick-borne encephalitis virus designated Zausaev (Za) was isolated in Siberia from a patient who died of a progressive (2-year) form of tick-borne encephalitis 10 years after being bitten by a tick. The complete genomic sequence of this virus was determined, and an attempt was made to correlate the sequence with the biological characteristics of the virus. Phylogenetic analysis demonstrated that this virus belongs to the Siberian subtype of Tick-borne encephalitis virus. Comparison of Za virus with two related viruses, a Far Eastern isolate, Sofjin, and a Siberian isolate, Vasilchenko, revealed differences among the three viruses in pathogenicity for Syrian hamsters, cytopathogenicity for PS cells, plaque morphology, and the electrophoretic profiles of virus-specific nonstructural proteins. Comparative amino acid alignments revealed 10 individual amino acid substitutions in the Za virus polyprotein sequence that were different from those of other tick-borne flaviviruses. Notably, the dimeric form of the Za virus NS1 protein migrated in polyacrylamide gels as a heterogeneous group of molecules with a significantly higher electrophoretic mobility than those of the Sofjin and Vasilchenko viruses. Two amino acid substitutions, T(277)-->V and E(279)-->G, within the NS1 dimerization domain are probably responsible for the altered oligomerization of Za virus NS1. These studies suggest that the patient from whom Za virus was isolated died due to increased pathogenicity of the latent virus following spontaneous mutagenesis.
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The neurovirulence and replication potential of several mumps virus strains, including Leningrad-3 mumps vaccine virus (FSUE SIC "Microgen", Russia) and wild type strains isolated in the Novosibirsk Region (Russia), were assessed in rat tests. The mean neurovirulence scores of the Leningrad-3 virus (