Characterization of a Novel Virus Causing a Lethal Disease in Carp and Koi

Since 1998 a lethal disease of carp and ornamental koi (Cyprinus carpio) has afflicted fisheries in North America, Europe, and Asia, causing severe economic losses to the fish farming industry. This review summarizes the isolation and identification of the disease-causing agent and describes the currently known molecular characteristics of this newly isolated virus, distinguishing it from other known large DNA viruses. In addition, we summarize the clinical and histopathological manifestations of the disease. Providing information on the immune response to this virus and evaluating the available means of diagnosis and protection should help to reduce the damage induced by this disease. This review does not discuss the economic aspects of the disease or the debate on whether the disease should be registered; both of these issues were recently reviewed in detail (O. L. M. Haenen, K. Way, S. M. Bergmann, and E. Ariel, Bull. Eur. Assoc. Fish Pathol. 24:293-307, 2004; D. Pokorova, T. Vesely, V. Piackova, S. Reschova, and J. Hulova, Vet. Med. Czech. 50:139-147, 2005).     

Identification of a uniquely immunodominant, cross-reacting site in the human immunodeficiency virus endonuclease protein.

One of the features of the life cycle of retroviruses is insertion of the proviral DNA into host chromosomes. A protein encoded by the 3' end of the pol gene of the virus genome has been shown to possess endonuclease activity (D. P. Grandgenett, A. C. Vora, and R. D. Schiff, Virology 89:119-132, 1978), which is necessary for DNA integration. Sera from the majority of human immunodeficiency virus (HIV)-infected individuals react with endonuclease protein p31 in serological tests (J. S. Allan, J. E. Coligan, T.-H. Lee, F. Barin, P. J. Kanki, S. M'Boup, M. F. McLane, J. E. Groopman, and M. Essex, Blood 69:331-333, 1987; E. F. Lillehoj, F. H. R. Salazar, R. J. Mervis, M. G. Raum, H. W. Chan, N. Ahmad, and S. Venkatesan, J. Virol. 62:3053-3058, 1988; K. S. Steimer, K. W. Higgins, M. A. Powers, J. C. Stephans, A. Gyenes, G. George-Nascimento, P. A. Liciw, P. J. Barr, R. A. Hallewell, and R. Sanchez-Pescador, J. Virol. 58:9-16, 1986). It is not known, however, which part of the protein represents the target(s) for antibody response. To study this, we synthesized peptides and used them in an enzyme-linked immunosorbent assay system to map the reactivity of human immunodeficiency virus type 1 (HIV-1) antibody-positive sera to the different regions of the HIV endonuclease. A uniquely antigenic, HIV-1- and HIV-2-cross-reacting site was identified in the central part of this protein from Phe-663 to Trp-670.     

Accomplishments and challenges in picornavirology as observed by a medical doctor

Background: The family of picornaviridae has been studied extensively: the structure of the virion and its replication strategy are known in molecular detail. Nevertheless, infections with the multitude of enteroviruses still cause widespread epidemics, serious disease and a diversity of clinical syndromes ranging from central nervous system involvement to light febrile illness. Infections with more than 100 human rhinovirus types are an important economic factor.Objective: In order to treat and control picornavirus infections with their great diversity of manifestations the pathogenesis of diseases must be better understood, e.g. concerning virus spread in the organism or molecular detail of the disease processes, such as cell tropism of the virus or cytokine and immunologic actions. Elucidation of mechanisms of virus transmission in the population is also needed.Study design: This review discusses aspects of our present knowledge of the pathogenesis, transmission, prophylaxis and treatment of picornavirus infections.Conclusions: The need for further development of selective antiviral substances, safe vaccines and basic research in picornavirology is stressed.     

Wiskott-Aldrich syndrome protein is needed for vaccinia virus pathogenesis

Smallpox, caused by variola virus, was a devastating disease in humans, but how the virus evolved a strategy to spread to tissue remains unknown. Through the use of microarrays, we identified the gene encoding the Wiskott-Aldrich syndrome protein (WASP), one of the five known WASP family members, which has been induced in the course of infection of human cells with different strains of vaccinia virus (VV) (S. Guerra, L. A. Lopez-Fernandez, A. Pascual-Montano, M. Munoz, K. Harshman, and M. Esteban, J. Virol. 77:6493-6506, 2003; S. Guerra, L. A. Lopez-Fernandez, R. Conde, A. Pascual-Montano, K. Harshman, and M. Esteban, J. Virol. 78:5820-5834, 2004). In a mouse model, we evaluated the role of WASP in infection with VV, a close relative of variola virus. WASP(-/-) (KO) mice infected intranasally and intraperitoneally with VV showed reduced weight loss and mortality compared to wild-type (WT) mice. WASP expression correlated with VV replication in the ovaries but not in the liver or spleen. WT mouse macrophages express WASP but not N-WASP; after VV infection, WASP levels increase threefold. KO macrophages lack N-WASP expression and, when VV infected, are incapable of inducing actin tails and producing extracellular virus. These functions were rescued in KO macrophages after ectopic WASP expression. Overall, our findings demonstrate that WASP has a role in orthopoxvirus infections. Use of WASP proteins for virus spread via the actin tail provides a selective advantage for VV, and probably variola virus, dissemination to distant tissues.     

Inhibition of different Lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus

The high pathogenicity of Lassa virus is assumed to involve resistance to the effects of interferon (IFN). We have analyzed the effects of alpha IFN (IFN-alpha), IFN-gamma, and tumor necrosis factor alpha (TNF-alpha) on replication of Lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (LCMV). Three low-passage Lassa virus strains (AV, NL, and CSF), isolated from humans with mild to fulminant Lassa fever, were tested. Lassa virus replication was inhibited by IFN-alpha and IFN-gamma, but not TNF-alpha, in Huh7 and Vero cells. The degree of IFN sensitivity of a Lassa virus isolate did not correlate with disease severity in human patients. Furthermore, cytokine effects observed for Lassa virus and LCMV (strains CH-5692, Armstrong, and WE) were similar. To address the mechanisms involved in the IFN effect, we used cell lines in which overexpression of IFN-stimulated proteins promyelocytic leukemia protein (PML) and Sp100 could be induced. Both proteins reside in PML bodies, a cellular target of the LCMV and Lassa virus Z proteins. Overexpression of PML or Sp100 did not affect replication of either virus. This, together with the previous finding that PML knockout facilitates LCMV replication in vitro and in vivo (M. Djavani, J. Rodas, I. S. Lukashevich, D. Horejsh, P. P. Pandolfi, K. L. Borden, and M. S. Salvato, J. Virol. 75:6204-6208, 2001; W. V. Bonilla, D. D. Pinschewer, P. Klenerman, V. Rousson, M. Gaboli, P. P. Pandolfi, R. M. Zinkernagel, M. S. Salvato, and H. Hengartner, J. Virol. 76:3810-3818, 2002), describes PML as a mediator within the antiviral pathway rather than as a direct effector protein. In conclusion, the high pathogenicity of Lassa virus compared to LCMV is probably not due to increased resistance to the effects of IFN-alpha or IFN-gamma. Both cytokines inhibit replication which is relevant for the design of antiviral strategies against Lassa fever with the aim of enhancing the IFN response.     

Influenza A Virus M2 Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

The amantadine-sensitive ion channel activity of influenza A virus M2 protein was discovered through understanding the two steps in the virus life cycle that are inhibited by the antiviral drug amantadine: virus uncoating in endosomes and M2 protein-mediated equilibration of the intralumenal pH of the trans Golgi network. Recently it was reported that influenza virus can undergo multiple cycles of replication without M2 ion channel activity (T. Watanabe, S. Watanabe, H. Ito, H. Kida, and Y. Kawaoka, J. Virol. 75:5656-5662, 2001). An M2 protein containing a deletion in the transmembrane (TM) domain (M2-del(29-31)) has no detectable ion channel activity, yet a mutant virus was obtained containing this deletion. Watanabe and colleagues reported that the M2-del(29-31) virus replicated as efficiently as wild-type (wt) virus. We have investigated the effect of amantadine on the growth of four influenza viruses: A/WSN/33; N31S-M2WSN, a mutant in which an asparagine residue at position 31 in the M2 TM domain was replaced with a serine residue; MUd/WSN, which possesses seven RNA segments from WSN plus the RNA segment 7 derived from A/Udorn/72; and A/Udorn/72. N31S-M2WSN was amantadine sensitive, whereas A/WSN/33 was amantadine resistant, indicating that the M2 residue N31 is the sole determinant of resistance of A/WSN/33 to amantadine. The growth of influenza viruses inhibited by amantadine was compared to the growth of an M2-del(29-31) virus. We found that the M2-del(29-31) virus was debilitated in growth to an extent similar to that of influenza virus grown in the presence of amantadine. Furthermore, in a test of biological fitness, it was found that wt virus almost completely outgrew M2-del(29-31) virus in 4 days after cocultivation of a 100:1 ratio of M2-del(29-31) virus to wt virus, respectively. We conclude that the M2 ion channel protein, which is conserved in all known strains of influenza virus, evolved its function because it contributes to the efficient replication of the virus in a single cycle.     

Assembly of viral membranes: nature of the association of vesicular stomatitis virus proteins to membranes.

To explore the interaction of vesicular stomatitis virus (VSV) proteins with cellular membranes, we have isolated membranes from infected cells that have been radioactively pulse-labeled. We have found conditions of isolation that result in membrane preparation which contain primarily the VSV membrane protein (M) and glycoprotein (G). Both of these proteins are very firmly attached to membranes: conditions known to release peripherally associated membrane proteins from membranes (S. Razin, Biochim, Biophys. Acta 265:241-246, 1972; S. J. Singer, Annu. Rev. Biochem. 43:805-826, 1974; S. J. Singer and G. L. Nicholson, Science 175:720-731, 1972) are ineffective in detaching either the G or the M protein. The results of trypsin digestion of these membrane fractions suggest that the M protein resides primarily on one side, the cytoplasmic side of cellular membranes, whereas the glycoprotein has been transported to the lumen of the membrane vesicle. However, we present evidence that the glycoprotein is transmembranal and that approximately 3,000 daltons of one end of the molecule is on the cytoplasmic side of the membrane. We have also found that undenatured VSV M protein contains a trypsin-resistant core with a molecular weight of 22,000. This region of the M protein is trypsin-resistant regardless of its association with membranes.     

Ngari virus is a Bunyamwera virus reassortant that can be associated with large outbreaks of hemorrhagic fever in Africa

Two isolates of a virus of the genus Orthobunyavirus (family Bunyaviridae) were obtained from hemorrhagic fever cases during a large disease outbreak in East Africa in 1997 and 1998. Sequence analysis of regions of the three genomic RNA segments of the virus (provisionally referred to as Garissa virus) suggested that it was a genetic reassortant virus with S and L segments derived from Bunyamwera virus but an M segment from an unidentified virus of the genus Orthobunyavirus. While high genetic diversity (52%) was revealed by analysis of virus M segment nucleotide sequences obtained from 21 members of the genus Orthobunyavirus, the Garissa and Ngari virus M segments were almost identical. Surprisingly, the Ngari virus L and S segments showed high sequence identity with those of Bunyamwera virus, showing that Garissa virus is an isolate of Ngari virus, which in turn is a Bunyamwera virus reassortant. Ngari virus should be considered when investigating hemorrhagic fever outbreaks throughout sub-Saharan Africa.     

Development and characterization of a recombinant infectious bronchitis virus expressing the ectodomain region of S1 gene of H120 strain

Infectious bronchitis (IB), caused by infectious bronchitis virus (IBV), is a highly contagious chicken disease, and can lead to serious economic losses in poultry enterprises. The continual introduction of new IBV serotypes requires alternative strategies for the production of timely and safe vaccines against the emergence of variants. Modification of the IBV genome using reverse genetics is one way to generate recombinant IBVs as the candidates of new IBV vaccines. In this study, the recombinant IBV is developed by replacing the ectodomain region of the S1 gene of the IBV Beaudette strain with the corresponding fragment from H120 strain, designated as rBeau-H120(S1e). In Vero cells, the virus proliferates as its parental virus and can cause syncytium formation. The peak titer would reach 10^5.9 50 % (median) tissue culture infective dose/mL at 24 h post-infection. After inoculation of chickens with the recombinant virus, it demonstrated that rBeau-H120(S1e) remained nonpathogenic and was restricted in its replication in vivo. Protection studies showed that vaccination with rBeau-H120 (S1e) at 7-day after hatch provided 80 % rate of immune protection against challenge with 10³ 50 % embryos infection dose of the virulent IBV M41 strain. These results indicate that rBeau-H120 (S1e) has the potential to be an alternative vaccine against IBV based on excellent propagation property and immunogenicity. This finding might help in providing further information that replacement of the ectodomain fragment of the IBV Beaudette S1 gene with that from a present field strain is promising for IBV vaccine development.     

Restricted virus replication in the spinal cords of nude mice infected with a Theiler''s virus variant.

The Daniels strain of Theiler's murine encephalomyelitis produces a chronic disease which is an animal model for human demyelinating disorders. Previously, we selected a neutralization-resistant virus variant producing an altered and diminished central nervous system disease in immunocompetent mice which was evident during the later stage of infection (after 4 weeks) (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). The exact epitope determining neurovirulence was precisely mapped to a capsid protein, VP-1, and represents a neutralizing region (A. Zurbriggen, J. M. Hogle, and R. S. Fujinami, J. Exp. Med. 170:2037-2049, 1989). Here, we present experiments with immunoincompetent animals to determine viral replication, spread, and targeting to the central nervous system in the absence of detectable antibodies or functional T cells. Nude mice were infected orally, and the virus was monitored by plaque assay, immunohistochemistry, and in situ hybridization. Early during the infection (1 week), the variant virus induced an acute disease comparable to that induced by the wild-type virus in these nude mice. Alterations in tropism in the central nervous system were not apparent when wild-type parental Daniels strain virus was compared with the variant virus. Moreover, variant virus replicated in tissue culture (BHK-21 cells) to similarly high titers in a time course identical to that of the wild-type virus (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). However, replication of the variant virus versus the wild-type virus within the spinal cord of athymic nude mice infected per os was substantially restricted by 6 weeks postinfection. Therefore, the reduced neurovirulence in the later stage (6 weeks) of the disease is most likely due to a diminished growth rate or spread of the variant virus in the central nervous system rather than to marked differences in viral tropism.     

Drosophila S virus is a member of the Reoviridae family

The S character of Drosophila simulans, the absence or malformation or both of bristles and other cuticular structures, was described by Comendador (Drosophila Inf. Serv. 55:26-28, 1980). Its characteristics (maternal transmission, low pathogenicity, and sensitivity to temperature) suggested the existence of a virus as the causative agent. Indeed, reoviruslike particles were found in subcuticular cells of S individuals, and its association with S phenotypic expression was shown. This virus was called Drosophila S virus (DSV) (C. Louis, M. López-Ferber, N. Plus, G. Kuhl, and S. Baker, J. Virol. 62:1266-1270, 1988). We report here the purification and analysis of some properties of DSV particles, the morphology (spherical, 60 nm in diameter with an electron dense central core and less dense shell) and genome composition (double-stranded RNA divided into segments), which classify DSV as a new member of the family Reoviridae.     

Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease

Fabry disease is a lysosomal storage disorder caused by an α-galactosidase A (α-Gal A) deficiency and resulting in the accumulation of glycosphingolipids, predominantly globotriaosylceramide (Gb3). A transgenic mouse expressing the human α-Gal A R301Q mutant in an α-Gal A-knockout background (TgM/KO) should be useful for studying active-site-specific chaperone (ASSC) therapy for Fabry disease. However, the Gb3 content in the heart tissue of this mouse was too low to detect an ASSC-induced effect. To increase the Gb3 levels in mouse organs, we created transgenic mice (TgG3S) expressing human α1,4-galactosyltransferase (Gb3 synthase). High levels of Gb3 were observed in all major organs of the TgG3S mouse. A TgG3S (+/-)M(+/-)/KO mouse was prepared by cross-breeding the TgG3S and TgM/KO mice and the Gb3 content in the heart of the TgG3S(+/-)M(+/-)/KO mouse was 1.4 μg/mg protein, higher than in the TgM(+/-)/KO (<0.1 μg/mg protein). Treatment with an ASSC, 1-deoxygalactonojirimycin, caused a marked induction of α-Gal A activity and a concomitant reduction of the Gb3 content in the TgG3S(+/-) M(+/-)/KO mouse organs. These data indicated that the TgG3S(+/-) M(+/-)/KO mouse was suitable for studying ASSC therapy for Fabry disease, and that the TgG3S mouse would be useful for studying the effect of high Gb3 levels in mouse organs.     

Independent evolution of monkeypox and variola viruses.

Smallpox was eradicated more than 10 years ago, but infection with another Orthopoxvirus, monkeypox virus, can result in a clinical picture resembling smallpox. Human infection with monkeypox virus is extremely rare, not easily transmitted, and confined to the rain forest belt of Africa (Z. Jezek and F. Fenner, p. 81-102, in Human Monkeypox, 1988). Evidence that variola virus, the causative agent of smallpox, might be readily derived from monkeypox virus was presented [S. S. Marennikova and E. M. Shelukhina, Nature (London) 276:291-292, 1978; S. S. Marennikova, E. M. Shelukhina, N. N. Maltseva, and G. R. Matsevich Intervirology 11:333-340, 1979], but this was not confirmed [K. R. Dumbell and L. C. Archard, Nature (London) 286:29-32, 1980] and was subsequently discounted (J. J. Esposito, J. H. Nakano, and J. F. Obijeski, Bull. W.H.O. 63:695-703, 1985). Although enough difference between the genomes of monkeypox and variola viruses to rule out a simple interconversion has been demonstrated [K. R. Dumbell and L. C. Archard, Nature (London) 286:29-32, 1980; J. J. Esposito and J. C. Knight, Virology 143:230-251, 1985; J. J. Esposito, J. H. Nakano, and J. F. Obijeski, Bull. W.H.O. 63:695-703, 1985; M. Mackett and L. C. Archard, J. Gen. Virol. 45:683-701, 1979], the possibility that monkeypox virus was a more remote ancestor of variola virus remained. We have now identified a sequence in monkeypox virus DNA which is a homolog of a 1,065-bp open reading frame in the conserved region of the variola virus genome but which has multiple deletions. This is strong evidence that monkeypox virus is not ancestral to variola virus and strengthens confidence in the long-term success of smallpox eradication.     

Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus.

The influenza A virus M2 integral membrane protein has ion channel activity that can be inhibited by the antiviral drug amantadine. Recently, a spirene-containing compound, BL-1743 (2-[3-azaspiro (5,5)undecanol]-2-imidazoline), that inhibits influenza virus growth was identified (S. Kurtz, G. Lao, K. M. Hahnenberger, C. Brooks, O. Gecha, K. Ingalls, K.-I. Numata, and M. Krystal, Antimicrob. Agents Chemother. 39:2204-2209, 1995). We have examined the ability of BL-1743 to inhibit the M2 ion channel when expressed in oocytes of Xenopus laevis. BL-1743 inhibition is complete as far as can be measured by electrophysiological methods and is reversible, with a reverse reaction rate constant of 4.0 x 10(-3) s(-1). In contrast, amantadine inhibition is irreversible within the time frame of the experiment. However, BL-1743 inhibition and amantadine inhibition have similar properties. The majority of isolated influenza viruses resistant to BL-1743 are also amantadine resistant. In addition, all known amino acid changes which result in amantadine resistance also confer BL-1743 resistance. However, one BL-1743-resistant virus isolated, designated M2-I35T, contained the change Ile-35-->Thr. This virus is >70-fold more resistant to BL-1743 and only 10-fold more resistant to amantadine than the wild-type virus. When the ion channel activity of M2-I35T was examined in oocytes, it was found that M2-I35T is BL-1743 resistant but is reversibly inhibited by amantadine. These findings suggest that these two drugs interact differently with the M2 protein transmembrane pore region.     

Alterations in Substrate Specificity and Physicochemical Properties of Deoxythymidine Kinase of a Drug-Resistant Herpes Simplex Virus Type 1 Mutant

The deoxythymidine kinase (dTK) activity of a 5-methoxymethyldeoxyuridine-resistant mutant (MMdU(r)-20) of herpes simplex virus type 1 was compared with that of the parental wild-type (WT) virus. The dTK activity induced by the mutant was consistently less than that induced by the WT virus, was inhibited by antibody specific for herpes simplex virus dTK, and was more thermostable than the WT dTK. Further, it was inhibited to a lesser degree than the WT dTK by the nucleoside analogs MMdU and arabinosylthymine (araT), which suggests that one of the effects of the mutation was a selective alteration in substrate recognition by the dTK. The loss of ability to inhibit the mutant dTK by E-(2)-5-bromovinyldeoxyuridine was not as great as that seen with araT and MMdU. This agrees well with our previous observation that the MMdU(r)-20 mutant of herpes simplex virus is only partially resistant to this analog, as compared with araT and MMdU (V. Veerisetty and G. A. Gentry, Virology 114:576-579, 1981). [2-(14)C]araT was used to explore further the resistance to araT. Extracts of cells infected with the mutant, although producing a small amount of [(14)C]araTMP, were unable to produce [(14)C]araTTP, in contrast to extracts of cells infected with the WT virus. Both extracts, however, produced [(14)C]dTTP from [(14)C]deoxyribosylthymine. Finally, the ability of the extracts to phosphorylate [(14)C]dTMP was examined. It was found that this activity was greatly reduced relative to dTK activity in the case of the mutant. These findings suggest that a mutation in the dTK polypeptide has affected recognition not only of nucleoside substrates but of the nucleotide substrate dTMP as well, which agrees with the suggestion of Chen et al. that both activities are located on the same polypeptide (M. S. Chen and W. H. Prusoff, J. Biol. Chem. 253:1325-1327, 1978; M. S. Chen, J. Walker, and W. H. Prusoff, J. Biol. Chem. 254:10747-10753, 1979; M. S. Chen, W. P. Summers, J. Walker, W. C. Summers, and W. H. Prusoff, J. Virol. 30:942-945, 1979).     

Identification of a sequence in the unique 5' open reading frame of the gene encoding glycosylated Gag which influences the incubation period of neurodegenerative disease induced by a murine retrovirus.

Neonatal inoculation of the wild-mouse ecotropic retrovirus CasBrE (clone 15-1) causes a noninflammatory spongiform neurodegenerative disease with an incubation period of > or = 6 months. Introduction of sequences from Friend murine leukemia virus (clone FB29) into the genome of CasBrE results in a marked shortening of the incubation period. The FB29 sequences which influence the incubation period were previously localized to the 5' leader sequence of the viral genome (M. Czub, F. J. McAtee, and J. L. Portis, J. Virol. 66:3298-3305, 1992). In the current study, we constructed a series of chimeric viruses consisting of the genome of CasBrE containing various segments of the leader sequence from FB29. A 41-nucleotide element (positions 481 through 521) near the 3' end of the leader was found to have a strong influence on the incubation period. This element influenced the kinetics of virus replication and/or spread in nonneuronal tissues, a property which was shown previously to determine the extent of central nervous system infection (M. Czub, F. J. McAtee, and J. L. Portis, J. Virol. 66:3298-3305, 1992). Curiously, this sequence had no demonstrable effect on virus replication in vitro in a fibroblastic cell line from Mus dunni. This segment encodes 14 of the unique 88-amino-acid N terminus of pr75gag, the precursor of a glycosylated form of the gag polyprotein which is expressed at the cell surface. Previous in vitro studies of mutants of Moloney murine leukemia virus lacking expression of glycosylated Gag failed to reveal a function for this protein in virus replication. We mutated the Kozak consensus sequence around the initiation codon for this protein in the chimeric virus CasFrKP, a virus which induces neurologic disease with a short (18- to 23-day) incubation period. M. dunni cells infected with the mutants lacked detectable cell surface Gag, but, compared with CasFrKP, no effect on replication kinetics in vitro was observed. In contrast, there was a marked slowing of the replication kinetics in vivo and a dramatic attenuation of neurovirulence. These studies indicate that glycosylated Gag has an important function in virus replication and/or spread in the mouse and further suggest that the sequence of its N terminus is a critical, though likely indirect, determinant of neurovirulence.     

拉沙热研究进展

拉沙热(Lassa fever,LF)由拉沙病毒(Lassa virus,LASV)引起,是一种通过鼠类传播给人的急性出血性动物源性传染病,病死率高。主要在西非地区流行,但在全球多个国家发现输入性病例。本文主要针对拉沙病毒的病原学特点、疾病流行现状、临床特征、实验室检测、治疗及预防进展进行综述。同时,建议在全球经济一体化的大形势下,加强对拉沙热国际防控的关注度,建立国际联防联控防治策略和措施,并将其纳入全球防控体系。     

A candidate for a new serotype of human rotavirus

We investigated genetic and serological characteristics of a human rotavirus isolate from Indonesia which had a "super short" RNA electrophoretic pattern (A. Hasegawa, S. Inouye, S. Matsuno, K. Yamaoka, R. Eko, and W. Suharyono, Microbiol. Immunol. 28:719-722, 1984). This virus, strain 69M, was found by RNA-RNA hybridization to have a low degree of homology with the representative strains of all four human serotypes. Furthermore, it could not be classified by neutralization analysis into any of these serotypes. Therefore, this virus might belong to a new serotype.     

Infectious diseases of the Pacific oyster,Crassostrea gigas

The Pacific oyster, Crassostrea gigas, is known for not having been affected by major epizootics of infectious diseases, unlike many other commercially important oysters worldwide. Nonetheless, review of the scientific literature reveals more than ten infectious diseases of this species including those with viral, bacterial, protozoan, and metazoan etiologies. These include diseases of larval, juvenile, and adult oysters. Diseases such as oyster velar virus disease, herpes-like infection, and ligament disease are known because of their importance in intensive husbandry systems of this bivalve. Nocardiosis, Marteilioides infection, haplosporidiosis, Denman Island disease, and others are primarily known from their effect on extensively cultured populations of the Pacific oyster. These diseases are reviewed in terms of their disease manifestations, etilogy, epizootiology and economic importance, prevention, and management and diagnosis.     

Molecular Mechanisms Involved in Antibody‐Dependent Enhancement of Dengue Virus Infection in Humans

Dengue is the most common arthropod‐borne viral infection in humans with ～50 million cases annually worldwide. In recent decades, a steady increase in the number of severe dengue cases has been seen. Severe dengue disease is most often observed in individuals that have pre‐existing immunity against heterotypic dengue subtypes and in infants with low levels of maternal dengue antibodies. The generally accepted hypothesis explaining the immunopathogenesis of severe dengue is called antibody‐dependent enhancement of dengue infection. Here, circulating antibodies bind to the newly infecting virus but do not neutralize infection. Rather, these antibodies increase the infected cell mass and virus production. Additionally, antiviral responses are diminished allowing massive virus particle production early in infection. The large infected cell mass and the high viral load are prelude for severe disease development. In this review, we discuss what is known about the trafficking of dengue virus in its human host cells, and the signalling pathways activated after virus detection, both in the absence and presence of antibodies against the virus. This review summarizes work that aims to better understand the complex immunopathogenesis of severe dengue disease.