- The role of infectious hematopoietic necrosis virus (IHNV) proteins in recruiting the ESCRT pathway through three ways in the host cells of fish during IHNV budding. [Journal Article]
- FSFish Shellfish Immunol 2019 Jul 09; 92:833-841
- In cytokinetic abscission, phagophore formation, and enveloped virus budding are mediated by the endosomal sorting complex required for transport (ESCRT). Many retroviruses and RNA viruses encode "la…
In cytokinetic abscission, phagophore formation, and enveloped virus budding are mediated by the endosomal sorting complex required for transport (ESCRT). Many retroviruses and RNA viruses encode "late-domain" motifs that can interact with the components of the ESCRT pathway to mediate the viral assembly and budding. However, the rhabdovirus in fish has been rarely investigated. In this study, inhibition the protein expression of the ESCRT components reduces the extracellular virion production, which preliminarily indicates that the ESCRT pathway is involved in IHNV release. The respective interactions of IHNV proteins including M, G, L protein with Nedd4, Tsg101, and Alix suggest the underlying molecular mechanism by which IHNV gets access to the ESCRT pathway. These results are the first observation that rhabdovirus in fish gains access to the ESCRT pathway through three ways of interactions between viral proteins and host proteins. In addition, the results show that IHNV is released from host cells through the ESCRT pathway. Taken together, our study provides a theoretical basis for studying the budding mechanism of IHNV.
- The Nucleoprotein and Phosphoprotein are Major Determinants of Virulence of Viral Hemorrhagic Septicemia Virus in Rainbow Trout. [Journal Article]
- JVJ Virol 2019 Jul 03
- Viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, infects several marine and freshwater fish species. There are many strains of VHSV that affect different fish, but some strains of one g…
Viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, infects several marine and freshwater fish species. There are many strains of VHSV that affect different fish, but some strains of one genetic subgroup have gained high virulence in rainbow trout (Oncorhynchus mykiss). To define the genetic basis of high virulence in trout, we used reverse genetics to create chimeric VHSVs in which viral N (nucleoprotein), P (phosphoprotein), or M (matrix protein) genes, or the N and P genes, were exchanged between a trout-virulent European VHSV strain (DK-3592B) and a trout-avirulent North American VHSV strain (MI03). Testing of the chimeric rVHSV by intraperitoneal injection in juvenile rainbow trout showed that exchanges of the viral P or M genes had no effect on the trout-virulence phenotype of either parental strain. However, reciprocal exchanges of the viral nucleoprotein (N) gene resulted in a partial gain-of-function in the chimeric trout-avirulent strain (22% mortality), and complete loss of virulence for the chimeric trout-virulent strain (2% mortality). Reciprocal exchanges of both the N and phosphoprotein (P) genes together resulted in complete gain-of-function in the chimeric avirulent strain (82% mortality), again with complete loss of virulence in the chimeric trout-virulent strain (0% mortality). Thus, the VHSV N gene contains an essential determinant of trout-virulence that is strongly enhanced by the viral P gene. We hypothesize that the host-specific virulence mechanism may involve increased efficiency of the viral polymerase complex when the N and P proteins have adapted to more efficient interaction with a host component from rainbow trout.IMPORTANCE Rainbow trout farming is a major food-source industry world-wide that has suffered great economic losses due to host jumps of fish rhabdovirus pathogens, followed by evolution of dramatic increases in trout-specific virulence. However, the genetic determinants of host jumps and increased virulence in rainbow trout are unknown for any fish rhabdovirus. Previous attempts to identify the viral genes containing trout-virulence determinants of viral hemorrhagic septicemia virus (VHSV) have not been successful. We show here that, somewhat surprisingly, the viral nucleocapsid (N) and phosphoprotein (P) genes together contain the determinants responsible for trout-virulence in VHSV. This suggests a novel host-specific virulence mechanism involving the viral polymerase and a host component. This differs from the known virulence mechanisms of mammalian rhabdoviruses based on the viral P or M (matrix) proteins.
- Sequencing, genome analysis and prevalence of a cytorhabdovirus discovered in Carica papaya. [Journal Article]
- PlosPLoS One 2019; 14(6):e0215798
- The complete genome of a new rhabdovirus infecting papaya (Carica papaya L.) in Ecuador, named papaya virus E, was sequenced and characterized. The negative-sense single-stranded RNA genome consists …
The complete genome of a new rhabdovirus infecting papaya (Carica papaya L.) in Ecuador, named papaya virus E, was sequenced and characterized. The negative-sense single-stranded RNA genome consists of 13,469 nucleotides with six canonical open reading frames (ORFs) and two accessory short ORFs predicted between ORFs corresponding to P3 (movement protein) and M (matrix protein). Phylogenetic analyses using amino acid sequences from the nucleocapsid, glycoprotein and polymerase, grouped the virus with members of the genus Cytorhabdovirus, with rice stripe mosaic virus, yerba mate chlorosis-associated virus and Colocasia bobone disease-associated virus as closest relatives. The 3' leader and 5' trailer sequences were 144 and 167 nt long, respectively, containing partially complementary motifs. The motif 3'-AUUCUUUUUG-5', conserved across rhabdoviruses, was identified in all but one intergenic regions; whereas the motif 3'-ACAAAAACACA-5' was found in three intergenic junctions. This is the first complete genome sequence of a cytorhabdovirus infecting papaya. The virus was prevalent in commercial plantings of Los Ríos, the most important papaya producing province of Ecuador. Recently, the genome sequence of bean-associated cytorhabdovirus was reported. The genome is 97% identical to that of papaya virus E, indicating that both should be considered strains of the same virus.
- Enhancement of oncolytic virotherapy by vanadium(V) dipicolinates. [Journal Article]
- BBiometals 2019; 32(3):545-561
- Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in re…
Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in responses suggesting that multiplexed approaches may be necessary to consistently generate positive outcomes in patients. To this end, we explored the combination of oncolytic rhabdovirus VSV∆51 with vanadium(V) dipicolinate derivatives, which have already been explored for their antidiabetic properties in animal models. The combination of vanadium-based dipicolinate compounds with VSV∆51 significantly increased viral replication and cytotoxicity in the human renal cell carcinoma cell line 786-0. The effects of three vanadium(V)-dipicolinate coordination complexes ([VO2dipic]-, [VO2dipic-OH]- and [VO2dipic-Cl]- with -OH or -Cl in the para position) were compared to that of the simple salts using spectroscopy and speciation profiles. Like the vanadate salts and the vanadyl cation, all dioxovanadium(V) dipicolinate complexes tested were found to increase viral infection and cytotoxicity when used in combination with VSV∆51. Viral sensitization is dependent on the vanadium since free dipicolinate ligands exerted no effect on viral infection and viability. The ability of these complexes to interact with interfaces and the stability of the complexes were evaluated under physiological conditions. Results indicate that these complexes undergo hydrolysis in cell culture media thereby generating vanadate. The vanadium dipicolinate derivatives in the context of immunovirotherapy shares similarities with previous studies exploring the antidiabetic properties of the compounds. The synergy between vanadium compounds and the oncolytic virus suggests that these compounds may be valuable in the development of novel and effective pharmaco-viral therapies.
- Entry of Challenge Virus Standard (CVS) -11 into N2a cells via a clathrin-mediated, cholesterol-, dynamin-, pH-dependent endocytic pathway. [Journal Article]
- VJVirol J 2019 Jun 13; 16(1):80
- CONCLUSIONS: Our results demonstrated that CVS-11 entered N2a cells through a clathrin-mediated, cholesterol-, pH-, dynamin-required, and caveolae-independent endocytic pathway.
- Temperature sensitivity and environmental stability of Chandipura virus. [Journal Article]
- VVirusdisease 2019; 30(2):214-218
- Chandipura virus (CHPV), a negative-stranded RNA virus of family Rhabdoviridae is endemic in Central India since 1965. The virus gained public health importance when it was held responsible for massi…
Chandipura virus (CHPV), a negative-stranded RNA virus of family Rhabdoviridae is endemic in Central India since 1965. The virus gained public health importance when it was held responsible for massive outbreak in 2003-2004 in Maharashtra, Telengana and Gujarat with case fatality rates ranging from 55 to 75% among children. We studied the stability of the virus as well as RNA persistence in samples stored at different temperatures for different periods. CHPV remained infective in sand flies and cell culture supernatants at 4 °C for 8 weeks. At 37 °C CHPV remained viable for 18 days when stored in infected cell supernatant (Minimum essential medium supplemented with 10% fetal bovine serum). However, in infected sand flies stored at 37 °C, the virus lost virulence within a week. CHPV RNA, though lost virulence, could be detected in virus exposed sand flies stored at 37 °C for 13 weeks by real time RT-PCR. Retaining virulence at 37 °C for 18 days in serum containing medium is a matter of concern for laboratories and hospital settings where clinical samples are handled. RNA persistence for prolonged periods in dead sand flies might help in surveillance studies of CHPV in sand flies and will help in resource constraint nations where cold chain management is a concern.
- [Epidemiological characteristics of human rabies in China, 2017]. [Journal Article]
- ZLZhonghua Liu Xing Bing Xue Za Zhi 2019 May 10; 40(5):526-530
- CONCLUSIONS: By 2017, the human rabies incidence in China had declined consecutively for ten years, more cases were reported in southern area than in northern area. The case number showed downward trends in provinces with high incidences and fluctuant increase in provinces with low incidence. Rabies cases mainly occurred in rural areas, and most cases were men and farmers. Low rate of post exposure prophylaxis, low rates of vaccination and passive immunization product injection were main causes for the onset of human rabies. It is necessary to strengthen the surveillance for human rabies, especially in rural areas, health education about treatment after rabies exposure and expend the coverage of canine immunization.
- The immunogenicity of the secretory GΔTM protein of bovine ephemeral fever virus stably expressed by mammalian cells. [Journal Article]
- VMVet Microbiol 2019; 233:113-117
- Bovine ephemeral fever virus (BEFV) causes an acute febrile disease in cattle and water buffalo. The disease has an impact on dairy and beef production in tropical and subtropical countries. Vaccinat…
Bovine ephemeral fever virus (BEFV) causes an acute febrile disease in cattle and water buffalo. The disease has an impact on dairy and beef production in tropical and subtropical countries. Vaccination is used for disease prevention and control. In this study, we developed a recombinant lentivirus to produce mammalian stable cells expressing histidine-tagged BEFV G protein with a deleted transmembrane domain (GΔTM) as a secretory protein. In addition, guinea pigs were immunised with the purified GΔTM protein and booster immunised at a 3-week interval. The mammalian stable cells were able to continuously produce GΔTM protein for a minimum of 25 passages. All of the mammalian stable cells expressing GΔTM protein could react specifically with a BEFV convalescent bovine serum. Serum samples from the immunised guinea pigs could react strongly and specifically with the purified GΔTM protein. Moreover, post-immunised guinea pig sera contained antibodies that could neutralise BEFV. These results indicate that the G protein without a transmembrane domain can be used as a subunit vaccine for the prevention and control of BEFV. The availability of the mammalian stable cells, which constitutively express GΔTM protein, could facilitate the potential use of the secretory protein for BEFV diagnosis and vaccine development.
- Method for serial passage of infectious hematopoietic necrosis virus (IHNV) in rainbow trout. [Journal Article]
- DADis Aquat Organ 2019 Jun 06; 134(3):223-236
- Transmission is a fundamental component of pathogen fitness. A better understanding of pathogen transmission can greatly improve disease management. In particular, controlled studies of multiple roun…
Transmission is a fundamental component of pathogen fitness. A better understanding of pathogen transmission can greatly improve disease management. In particular, controlled studies of multiple rounds of natural transmission (i.e. serial passage) can provide powerful epidemiological and evolutionary inferences. However, such studies are possible in only a few systems because of the challenges in successfully initiating and maintaining transmission in the laboratory. Here we developed an efficient and reproducible cohabitation method for conducting controlled experiments investigating the effects of serial passage on infectious hematopoietic necrosis virus (IHNV) in rainbow trout. This method was used to investigate the transmission efficiency and kinetics of viral shedding of IHNV over 3 serial passages. Transmission efficiency decreased from 100 to 62.5% over the passage steps and was associated with a decrease in virus shedding into water. A shift in the peak of viral shedding was also observed, from Day 2 post immersion for passage 0 to at least 24 h later for all subsequent passages. Finally, the characterization of viruses after 1 round of transmission and propagation on cells showed no change in glycoprotein (G gene) sequences or viral virulence compared to the ancestral virus stock. The methods developed provide valuable tools for reproducible population-level studies of IHNV epidemiology and evolution.
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- Current status of human rabies prevention: remaining barriers to global biologics accessibility and disease elimination. [Journal Article]
- ERExpert Rev Vaccines 2019; 18(6):629-640
- Introduction: Rabies is a serious, neglected tropical disease. Zoonotic agents are RNA viruses (Genus Lyssavirus, Family Rhabdoviridae), global in distribution. As an acute, progressive, incurable en…
Introduction: Rabies is a serious, neglected tropical disease. Zoonotic agents are RNA viruses (Genus Lyssavirus, Family Rhabdoviridae), global in distribution. As an acute, progressive, incurable encephalitis, rabies has the highest case fatality of any infectious disease. Warm-blooded vertebrates are susceptible hosts. Major mammalian reservoirs include mesocarnivores and bats. Given wildlife perpetuation, rabies is not eradicable, but is preventable and controllable, especially under newly available international guidelines. Areas covered: Literature review over the past 5 years reveals development of sensitive, specific diagnostic tests and safe and highly effective human and veterinary vaccines. Yet, tens of thousands of human fatalities occur annually, usually in Africa and Asia, primarily after canine exposure. Human and domestic animal vaccination, before or after exposure, is the single greatest preventative strategy following a rabid animal bite. Expert opinion: Significant progress occurred during the twenty-first century regarding vaccine development, doses, and schedules. Remaining barriers to widespread rabies vaccination include an inter-related set of economic, cultural, social, educational, ecological and technological factors. A basic understanding of local and regional root causes of cases historically allows for broader accessibility to vaccination in a trans-disciplinary fashion to meet the global elimination of human rabies caused via dogs (GEHRD) by 2030.