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Virology Journal Dec 2019Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often... (Review)
Review
Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Marburg Virus Disease; Marburgvirus
PubMed: 31888676
DOI: 10.1186/s12985-019-1272-z -
Viruses Oct 2021Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from...
Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain. These systems were generated starting solely with in silico genome sequence information and have been used successfully to produce recombinant stocks of each of the viruses for use in MCM testing. The antiviral activity of MCMs targeting viral entry varied depending on the recombinant virus isolate used. Collectively, selecting and synthetically engineering emerging EBOV variants and demonstrating their efficacy against available MCMs will be crucial for answering pressing public health and biosecurity concerns during Ebola disease (EBOD) outbreaks.
Topics: Cell Line; Disease Outbreaks; Ebolavirus; Genome, Viral; Genotype; Hemorrhagic Fever, Ebola; Humans; Medical Countermeasures; Phenotype; Phylogeny; Reverse Genetics
PubMed: 34696439
DOI: 10.3390/v13102010 -
Viruses Dec 2021Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV),... (Review)
Review
Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV), which are the major cause of severe acute respiratory tract illness in young children worldwide, and main pathogens infecting elderly and immune-compromised people. The transcription and replication of these viruses take place in specific cytoplasmic inclusions called inclusion bodies (IBs). These activities depend on viral polymerase L, associated with its cofactor phosphoprotein P, for the recognition of the viral RNA genome encapsidated by the nucleoprotein N, forming the nucleocapsid (NC). The polymerase activities rely on diverse transient protein-protein interactions orchestrated by P playing the hub role. Among these interactions, P interacts with the NC to recruit L to the genome. The P protein also plays the role of chaperone to maintain the neosynthesized N monomeric and RNA-free (called N) before specific encapsidation of the viral genome and antigenome. This review aims at giving an overview of recent structural information obtained for hRSV and hMPV P, N, and more specifically for P-NC and N-P complexes that pave the way for the rational design of new antivirals against those viruses.
Topics: Animals; Antiviral Agents; Drug Design; Humans; Metapneumovirus; Models, Molecular; Nucleocapsid Proteins; Paramyxoviridae Infections; Phosphoproteins; Protein Binding; Protein Conformation; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 34960719
DOI: 10.3390/v13122449 -
Frontiers in Immunology 2023Cancer incidence and mortality are increasing rapidly worldwide, necessitating further investigation into developing and optimizing emergent cancer therapies. Oncolytic...
BACKGROUND
Cancer incidence and mortality are increasing rapidly worldwide, necessitating further investigation into developing and optimizing emergent cancer therapies. Oncolytic viruses such as vesicular stomatitis virus encoding interferon β (VSV-IFNβ) have attracted considerable attention, as they offer great efficacy and safety profiles. This systematic review aimed to determine and compare the efficacy profile between VSV-IFNβ and non-treatment controls in preclinical cancer models.
METHODOLOGY
The Embase and Medline databases were systematically searched for relevant studies using related key terms and Medical Subject Headings (MeSH). Titles, abstracts, and full texts were screened, and data from eligible articles were extracted by two groups independently and in duplicate (two reviewers per group). Disagreements were resolved by a fifth independent reviewer. The included articles were all preclinical (translational) English studies that investigated and compared the efficacy profile between VSV-IFNβ and non-treatment controls in animal models. The risk of bias among the studies was assessed by two reviewers independently and in duplicate using SYRCLE's risk-of-bias tool for animal studies; disparities were addressed by a third independent reviewer.
RESULTS
After employing relevant MeSH and key terms, we identified 1598 articles. A total of 87 articles were either duplicates or conference proceedings and were thus excluded. Following title and abstract screening, 37 articles were included in the full-text assessment. Finally, 14 studies met the eligibility criteria. Forty-two experiments from the included studies examined the potential efficacy of VSV-IFNβ through different routes of administration, including intratumoral, intraperitoneal, and intravenous routes. Thirty-seven experiments reported positive outcomes. Meanwhile, five experiments reported negative outcomes, three and two of which examined intratumoral and intravenous VSV-IFNβ administration, respectively.
CONCLUSION
Although the majority of the included studies support the promising potential of VSV-IFNβ as an oncolytic virus, further research is necessary to ensure a safe and efficacious profile to translate its application into clinical trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022335418.
Topics: Animals; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Vesicular stomatitis Indiana virus; Vesiculovirus; Interferon-beta
PubMed: 37063914
DOI: 10.3389/fimmu.2023.1085940 -
Viruses Dec 2023Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and... (Review)
Review
Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and Nipah virus are the most notable henipaviruses, resulting in significant outbreaks across South Asia, South-East Asia, and Australia. Pteropid fruit bats have been identified as key zoonotic reservoirs; however, the increased discovery of henipaviruses outside the geographic distribution of Pteropid fruit bats and the detection of novel henipa-like viruses in other species such as the shrew, rat, and opossum suggest that Pteropid bats are not the sole reservoir for henipaviruses. In this review, we provide an update on henipavirus spillover events and describe the recent detection of novel unclassified henipaviruses, with a strong focus on the shrew and its emerging role as a key host of henipaviruses.
Topics: Humans; Animals; Rats; Henipavirus Infections; Shrews; Chiroptera; Nipah Virus; Hendra Virus
PubMed: 38140648
DOI: 10.3390/v15122407 -
Molecular Biology and Evolution Mar 2021Phylogenetic trees inferred from sequence data often have branch lengths measured in the expected number of substitutions and therefore, do not have divergence times...
Phylogenetic trees inferred from sequence data often have branch lengths measured in the expected number of substitutions and therefore, do not have divergence times estimated. These trees give an incomplete view of evolutionary histories since many applications of phylogenies require time trees. Many methods have been developed to convert the inferred branch lengths from substitution unit to time unit using calibration points, but none is universally accepted as they are challenged in both scalability and accuracy under complex models. Here, we introduce a new method that formulates dating as a nonconvex optimization problem where the variance of log-transformed rate multipliers is minimized across the tree. On simulated and real data, we show that our method, wLogDate, is often more accurate than alternatives and is more robust to various model assumptions.
Topics: Algorithms; Ebolavirus; Genetic Techniques; Influenza A Virus, H1N1 Subtype; Mutation Rate; Phylogeny
PubMed: 32886788
DOI: 10.1093/molbev/msaa222 -
The Journal of General Virology Nov 2021is a family of viruses in the order , with unsegmented (except for members of the genus ), negative-sense RNA genomes of 10-13 kb. Nyamviruses have a genome...
is a family of viruses in the order , with unsegmented (except for members of the genus ), negative-sense RNA genomes of 10-13 kb. Nyamviruses have a genome organisation and content similar to that of other mononegaviruses. includes several genera that form monophyletic clades on phylogenetic analysis of the RNA polymerase. Nyamiviruses have been found associated with diverse invertebrates as well as land- and seabirds. Members of the genera and produce enveloped, spherical virions. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family which is available at ictv.global/report/nyamiviridae.
Topics: Animals; Genome, Viral; Invertebrates; Mononegavirales; Phylogeny; RNA, Viral; Viral Proteins; Virion
PubMed: 34738886
DOI: 10.1099/jgv.0.001681 -
Jornal de Pediatria 2023To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and... (Review)
Review
OBJECTIVE
To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries.
METHODS
The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757.
RESULTS
No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed.
CONCLUSION
The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.
Topics: Humans; Child; Infant; Developing Countries; Financial Stress; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Parainfluenza Virus 3, Human; Hospitalization
PubMed: 37247828
DOI: 10.1016/j.jped.2023.05.003 -
Viruses Dec 2022Ebola (EBOV) and Marburg virus (MARV) are highly pathogenic filoviruses that influence cellular signaling according to their own needs. MARV has been shown to regulate...
Ebola (EBOV) and Marburg virus (MARV) are highly pathogenic filoviruses that influence cellular signaling according to their own needs. MARV has been shown to regulate the IRE1α-dependent unfolded protein response (UPR) to ensure optimal virus replication. It was not known whether EBOV affects this signaling cascade, which can be beneficial or detrimental for viruses. Activation of IRE1α leads to the expression of the transcription factor XBP1s, which binds to cis-acting UPR elements (UPRE), resulting in the expression of genes aimed at restoring homeostasis in the endoplasmic reticulum. We observed that EBOV infection, in contrast to MARV infection, led to UPR activation by IRE1α-dependent but not ATF6-dependent signaling. We showed an activation of IRE1α, XBP1s and UPRE target genes upon EBOV infection. ATF6, another UPRE transcription factor, was not activated. UPRE activation was mainly attributed to the EBOV nucleoprotein NP and the soluble glycoprotein sGP. Finally, activation of UPR by thapsigargin, a potent ER-stress inducer, in parallel to infection as well as knock-out of XBP1 had no effect on EBOV growth, while MARV proliferation was affected by thapsigargin-dependent UPR activation. Taken together EBOV and MARV differ in their strategy of balancing IRE1α-dependent signaling for their own needs.
Topics: Humans; Ebolavirus; Endoplasmic Reticulum Stress; Endoribonucleases; Hemorrhagic Fever, Ebola; Marburgvirus; Protein Serine-Threonine Kinases; Thapsigargin; Transcription Factors; Unfolded Protein Response
PubMed: 36680162
DOI: 10.3390/v15010122 -
Viruses May 2020Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including... (Review)
Review
Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the genus within the family. FeMV research has focused primarily on determining the host range, symptoms, and characteristics of persistent infections in vitro. Importantly, there is a potential association between FeMV infection and feline kidney diseases, such as tubulointerstitial nephritis (TIN) and chronic kidney diseases (CKD), which are known to significantly affect feline health and survival. However, the tropism and viral entry mechanism(s) of FeMV remain unknown. In this review, we summarize the FeMV studies up to date, including the discoveries of various FeMV strains, basic virology, pathogenicity, and disease signs.
Topics: Animals; Cat Diseases; Cats; Kidney Diseases; Morbillivirus; Morbillivirus Infections; Paramyxoviridae
PubMed: 32370044
DOI: 10.3390/v12050501