SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism

Newcastle disease virus (NDV), a member of the family Paramyxoviridae causes an acute and highly contagious disease mainly affecting chickens and turkeys. The virus causes significant changes in metabolism of amino acids in the host cells, with glutamic acid being the most upregulated followed by aspartic acid. This study also showed that the five Solute carrier family 1 (SLC1) members that are high-affinity glutamate transporters, SLC1A3 was the most significantly upregulated during NDV replication. The use of siRNA knockdown of SLC1A3 resulted in significant reduction in expression of the NDV nucleoprotein and NDV titer in the cells and cell supernatant respectively. This clearly demonstrated that SLC1A3 is indispensable in NDV replication. To determine which amino acids are indispensable for NDV replication, the glucose-enriched growth media were prepared with and without glutamine and the results indicated that NDV only replicates when the amino acid glutamine is present. SLC1A3 promotes glutamine uptake and catabolism, which promotes NDV replication in the infected cells. This experiment shows how NDV hijacks cellular SLC1A3 to its own advantage of replicating.
(WWN)

Crimean-Congo Hemorrhagic Fever Virus Seropositivity among Dromedary Camels, Algeria, 2020-2021

Crimean-Congo Hemorrhagic Fever Virus, a member of the genus Orthonairovirus in the family Nairoviridae, is a tick borne virus that causes the Crimean-Congo Hemorrhagic Fever, a systemic disease capable of causing death among infected individuals. Wild and domestic animals maintain the virus in the ecosystem because they may harbour the ticks that transmit this disease to humans. This is a serosurveilance study that sought to determine the prevalence and risk factors for the disease among the widely kept dromedary camels in the northeastern Saharan region of Algeria. From the 294 serum samples collected, the prevalence of antibodies against the virus was 75.5% and 95.7% at animal and herd levels respectively. Significant risk factors for the disease among the dromedaries were traditional and semi-traditional rearing systems and old age above 4 years. This study shows how the human population in Algeria is at a high risk of contracting the viral disease due to their close contact with the dromedaries, from which this study revealed high prevalence.

(WWN)

The mechanism of genome replication and transcription in bunyaviruses

Bunyaviruses are negative-strand RNA viruses that have an envelope and segments. The virion structure is relatively simple, consisting of a nucleocapsid (N) protein and two transmembrane glycoproteins (Gn and Gc). The Bunyavirales is currently split into fourteen virus families, including Peribunyaviridae, Phenuiviridae, Nairoviridae, Hantaviridae, Tospoviridae, and Arenaviridae. The virion also contains RNA-dependent RNA polymerase (L polymerase). Bunyaviruses undergo a replication cycle similar to other negative-strand RNA viruses. Many structures of bunyavirus L proteins have been solved in recent years, thanks to advancements in cryogenic electron microscopy technology. These structures greatly improve our mechanistic understanding of bunyavirus genome replication and transcription processes, as well as highlighting differences and similarities among bunyavirus L proteins from various families. The characterization of the structure and function of the L protein has advanced significantly in recent years, providing new information on the complex biological processes underlying transcription and replication of the bunyavirus genome. The emergence of these novel structural data indicates a new era in bunyavirus research, where structural data or structure predictions may enhance functional investigations on transcription and genome replication.
(HR)

Self-amplifying RNA vaccine protects mice against lethal Ebola virus infection

The Zaire Ebola virus (EBOV) is a member of the family Filoviridae, and causes an average case fatality ratio of 50% among the infected population. The viral genome encodes for seven structural proteins: the nucleoprotein NP, VP35, VP30, VP24, and the polymerase L forming the nucleocapsid, and VP40 forming a matrix layer around the nucleocapsid and is associated with the viral lipid envelope into which the surface glycoprotein GP is inserted. In this study, self-amplifying RNAs expressing the EBOV GP alone or in combination with the NP were constructed and tested in mice against EBOV. The mice were first vaccinated intramuscularly with a vaccine containing either GP or NP alone or a combination of GP and NP. This was followed by an infection with a lethal dose of EBOV days later. Results showed that mice that received either GP alone or GP+NP combination had more IgG levels in their serum compared to the mice that received the NP alone vaccine. Furthermore, the GP alone and GP+NP vaccines provided protection against EBOV but not the NP alone vaccine. The experiment also showed that intramuscular administration of the vaccine conferred better protection compared to intradermal route.
(WWN)

The MVA vector expressing the F protein of bovine respiratory syncytial virus is immunogenic in systemic and mucosal immunization routes

Bovine respiratory syncytial virus (BRSV), a member of the Pneumoviridae family, affects both the dairy and beef industry. The disease has a morbidity of 60-80% and mortality rate of about 20%; mainly affecting calves. The disease is spread via direct contact between the infected and the non-infected cattle and predispose the affected animals to secondary bacterial infections resulting in serious pneumonia. Because of its direct and indirect impact on the cattle industry, vaccines have been developed against the disease. However, there is failure to provide complete immunity because they usually interfere with maternal antibodies in calves and also result in severe enhanced respiratory disease. This study focused on developing a vaccine- the Modified vaccinia virus Ankara (MVA) expressing the fusion, F, protein of the BRSV virus using the Balb/C mice as the model. The vaccine was developed by transfecting the transfer vector containing the F protein of the BRSV into chicken embryo fibroblasts containing the MVA. Two routes of administration were employed in the study: intraperitoneal, in which both MVA-F homologous and heterologous vaccines were used and the intranasal (IN) route. The results of the study showed that IN administration of the MVA-F vaccine causes significant production of anti-BRSV IgA both in nasal mucosal washings and serum compared to the control group. Intraperitoneal administration of the MVA-F vaccine also yields significant anti-BRSV antigens and IFN-γ. These results indicate that when we combine the intranasal and intaperitoneal administration of MVA-F vaccine, there is both local and systemic immune responses which could potentially confer protection against BRSV
(WWN)

A comprehensive list of the Bunyavirales replication promoters reveals a unique promoter structure in Nairoviridae differing from other virus families

The Bunyavirales, a diverse order of viruses, infect various hosts, posing a notable public health threat. Featuring tri-segmented negative-sense RNA genomes, the order's major families exhibit replication promoters at their 5′ and 3′ ends. Understanding how viral polymerases initiate RNA synthesis through these promoters is vital for comprehending replication, pathogenesis, and antiviral development. Using public sequence data, the authors compiled a comprehensive list of bunyavirus replication promoters, revealing distinctive patterns in the 40-nucleotide segments at both ends of the genome. Particularly, the Nairoviridae family, housing the highly pathogenic Crimean-Congo hemorrhagic fever virus, showcases a unique GC-rich promoter structure not found in other families. The nucleotide variation in the promoter region of the Nairoviral L segment differed from that of the M and S segments. Specifically, a lower abundance of G and C was observed at the 5′ and 3′ ends, respectively. This distinction may relate to Nairoviridae's larger genome size, potentially granting pathogenic advantages. The provided replication promoter list is a valuable tool for predicting bunyavirus family-specific replication mechanisms.
(LA)

Host Responses to Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is a widespread respiratory virus that often causes mild, cold-like symptoms. Most patients recover within a week or two, but RSV can be dangerous. It is an enveloped negative sense RNA virus from the Orthopneumovirus genus of the Pneumoviridae family. The viral genome contains ten genes that encode eleven proteins: nonstructural proteins 1 and 2 (NS1/2), nucleocapsid protein (N), matrix protein (M), phosphoprotein (P), small hydrophobic protein (SH), glycoprotein (G), fusion protein (F), large protein (L), and M2, which has two overlapping open reading frames that result in two proteins, M2-1 and M2-2. Prophylactic administration of virus-neutralizing human monoclonal antibodies directed to the F protein, such as Synagis® (Palivizumab) and Beyfortus® (Nirsevimab), has been shown to reduce the risk of ALRI in high-risk neonates. However, developing a vaccination for RSV has been difficult. Following decades of research, two RSV vaccinations have been authorized to prevent lower respiratory tract infections in older persons. The FDA has licensed a vaccine for active vaccination of pregnant women to protect infants from severe RSV disease during their first RSV season.

(HR)

Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control

The Ebola virus is a member of the Filoviridae family. The Filoviridae viruses are RNA viruses with a negative strand. They are the most prevalent pathogens to infect humans and primates, causing lethal hemorrhagic fever. Ebolaviruses are classified into five subtypes based on where they were discovered: Zaire, Bundibugyo, Sudan, Reston, and Tai Forest. Ebola virus disease, formerly known as Ebola hemorrhagic fever, is defined by the classic hemorrhagic fever. The case mortality rate ranges from 25% to 90%, with an average of around 50%. Because of the increased frequency of Ebola virus disease outbreaks, early detection is critical for reducing the danger of an epidemic. Several preventative measures, including the development of a vaccine and quick testing using immunoassays or real-time polymerase chain reaction, were implemented in an attempt to limit the chance of a worldwide pandemic or exhausting epidemic. Today's epidemic management processes are mostly "reactive," with containment measures aimed at preventing the spread of existing epidemics. At present, no globally authorized therapy or vaccination available.
(HR)

Paramyxoviruses: Pathogenesis, Vaccines, Antivirals, and Prototypes for Pandemic Preparedness

Many paramyxoviruses cause a wide range of mild to severe human and animal diseases. Based on recent discoveries, the family Paramyxoviridae infects a variety of hosts around the world, including the measles virus, mumps virus, parainfluenza virus, and respiratory syncytial virus. The high rate of human-to-human transmission of paramyxoviruses like measles virus, the high case fatality rate associated with other family members like Nipah virus, and the presence of poorly characterized zoonotic pathogens all raise concerns that known and unknown paramyxoviruses have significant pandemic potential. Transmission occurs through direct touch or droplets. The virus attacks the respiratory mucosa's ciliated epithelial cells and spreads locally. immunopathologic antibody-dependent cellular cytotoxicity contributes to disease. In terms of biological features, the antigenic distance and, in particular, the low homology of available sequences. However, there are no effective licensed antiviral therapies or vaccines to treat the bulk of paramyxoviral infections, and we are woefully unprepared if a respiratory paramyxovirus emerges and spreads in humans with no prior immunization.
(HR)

Rhabdoviruses as Vectors for Vaccines and Therapeutics

Rhabdovirus is a Mononegavirales prototype with a single negative-strand RNA genome. The Rhabdoviridae family includes vesicular stomatitis virus (VSV) and the rabies virus (RABV). Rhabdoviruses typically contain five proteins: a large protein (L), a glycoprotein (G), a nucleoprotein (N), a phosphoprotein (P), and a matrix protein (M). The glycoprotein contains neutralizing epitopes that are targets of vaccine-induced immunity. RABV and VSV are both promising vaccine vector possibilities. Both RABV and VSV have been extensively explored and have well-established reverse genetics recovery techniques that can be combined with genome manipulation. This allows for the production of foreign genes and their integration into Rhabdovirus virions. Both vectors have shown to be effective vaccine vectors, as seen by the widespread use of the rabies vaccine and the FDA's clearance of VSV-ZEBOV. Furthermore, the safety profiles of both vectors for administration and manufacture are excellent. Therefore, these viruses have many uses despite other restrictions and the requirement to handle live viruses during manufacture. 

(HR)

Structures and Mechanisms of Nonsegmented, Negative-Strand RNA Virus Polymerases

Negative-strand RNA viruses are a diverse group of animal viruses that include a number of significant human diseases. Negative-strand RNA viruses with segmented or non-segmented genomes are to blame for a variety of serious viral illnesses. The sequence of the negative strand of RNA is complementary to that of the coding strand. Therefore, when entering the host cell, viruses carrying this genome must produce the corresponding plus strand. Recent and upcoming disease management approaches include siRNA (silencing RNA) technology to target viral genes, novel drug delivery approaches to improve the efficacy of previously approved FDA drugs, and the acquisition of novel approaches to developing host immunity against these viral diseases by primarily targeting viral RNA-dependent RNA polymerases.
(HR)

Reverse genetics approaches for the development of bunyavirus vaccines

Large number of RNA viruses belongs to the Bunyavirales order. There are serious diseases producing important human and animal pathogens. Few of these pathogens are often available in market available licensed vaccine. The formulations of bunyavirus reverse genetics systems act as understanding bunyavirus biology and identifying important virulence factors. The developing of novel strategies, including codon-deoptimization, viral genome rearrangement and single-cycle replicable viruses have established by technological advances, for the stage of life of live-attenuated vaccine candidates. In that reviewed, researcher had summarized the present knowledge of the bunyavirus reverse genetics approaches for the generation of live-attenuated vaccine candidates and their evaluation in animal models.
(RA)

Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection

Younger than 2 years old children affected with acute respiratory tract infections (ARTIs) caused by human respiratory syncytial virus (hRSV) world widely. In every year, a lot of hRSV-induced bronchitis & pneumonic patients are hospitalized during winter season. To prevent hRSV infection induced health and economic burden, there are no available vaccine in market. Pathology of hRSV is significant damage of pulmonary epithelium due to excessive inflammatory response at the airways. Cytokines can be beneficial or harmful for the host but they play a major role to establishment and modulation of the immune and inflammatory responses. The harmful effect detected in hRSV infection is tissue damage caused by aggregation of immune cell on the site of infection. Placing of Inflammatory cells are depends on, quantity of cytokines such as IL-1, IL-6, IL-10, and CCL5 are increased, while IL-10 and IFN-γ are decreased. Although, further studies are needed to draw out what are directly involved mediators associated with hRSV damage entirely. However, another report indicating that this virus not only affected respiratory tract but also affected central nervous system (CNS). A published report mentioned that highest levels of IL-6, IL-8 (CXCL8), CCL2, and CCL4 have been reported in cerebrospinal fluid from patients with severe bronchiolitis and hRSV-associated encephalopathy. In that review article, researcher provided the role of cytokines, secreted during hRSV infection and their potentially harmful contribution to tissue damage of the respiratory tract and the CNS.
(RA)

Borna disease virus docks on neuronal DNA double-strand breaks to replicate and dampens neuronal activity

Borna disease viruses (BoDV), which have emerged as zoonotic neurotropic pathogens, exhibit persistent RNA characteristics and form nuclear replication centers (vSPOT) closely interacting with the host chromatin. Despite this interaction, the exact nature of its topology and the resulting impact on neuronal function remain unexplored. Within neurons, the discovery of DNA double-strand breaks (DSB) has unveiled novel epigenetic mechanisms governing neurotransmission and cognition. These activity-dependent DSBs play a crucial role in neuronal plasticity, potentially affected during infection. This study demonstrates that BoDV-1 infection or the isolated expression of viral nucleoprotein and phosphoprotein elevates levels of neuronal DSBs. Intriguingly, inducing DSBs facilitates renewed recruitment of vSPOT, which co-localizes with DSBs, thereby enhancing viral RNA replication. Persistent BoDV-1 presence reduces neuronal activity and responsiveness to stimulation by diminishing the surface expression of glutamate receptors. In conclusion, the findings suggest a novel mechanistic interplay between RNA virus persistence and neuronal function, mediated through the regulation of DSB levels.
(LA)