Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study.

With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-ß-cyclodextrin (MßCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

Novel statistics predict the COVID-19 pandemic could terminate in 2022.

Many people want to know when the COVID-19 pandemic will end and life will return to normal. This question is highly elusive and distinct predictions have been proposed. In this study, the global mortality and case fatality rate of COVID-19 were analyzed using nonlinear regression. The analysis showed that the COVID-19 pandemic could terminate in 2022, but COVID-19 could be one or two times more deadly than seasonal influenza by 2023. The prediction considered the possibility of the emergence of new variants of SARS-CoV-2 and was supported by the features of the Omicron variant and other facts. As the herd immunity against COVID-19 established through natural infections and mass vaccination is distinct among countries, COVID-19 could be more or less deadly in some countries in the coming years than the prediction. Although the future of COVID-19 will have multiple possibilities, this statistics-based prediction could aid to make proper decisions and establish an example on the prediction of infectious diseases.

Should the world collaborate imminently to develop neglected live-attenuated vaccines for COVID-19?

The rapid spread of the Delta variant suggests that SARS-CoV-2 will likely be rampant for months or years and could claim millions of more lives. All the known vaccines cannot well defeat SARS-CoV-2 due to their limited efficacy and production efficiency, except for the neglected live-attenuated vaccines (LAVs), which could have a much higher efficacy and much higher production efficiency than other vaccines. LAVs, like messiahs, have defeated far more pathogenic viruses than other vaccines in history, and most current human vaccines for viral diseases are safe LAVs. LAVs can block completely infection and transmission of relevant viruses and their variants. They can hence inhibit the emergence of vaccine-escape and virulence-enhancing variants and protect immunologically abnormal individuals better in general. The safety of COVID-19 LAVs, which could save millions of more lives, can be solidly guaranteed through animal experiments and clinical trials. The safety of COVID-19 LAVs could be greatly enhanced with intramuscular or oral administration, or administration along with humanized neutralizing monoclonal antibodies. Together, extensive global collaboration, which can greatly accelerate the development of safe COVID-19 LAVs, is imminently needed.

A highly powerful nonspecific strategy to reduce COVID-19 deaths.

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.

Highly adaptive Phenuiviridae with biomedical importance in multiple fields.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis.

SARS-CoV-2 replicating in nonprimate mammalian cells probably have critical advantages for COVID-19 vaccines due to anti-Gal antibodies: A minireview and proposals.

Glycoproteins of enveloped viruses replicating in nonprimate mammalian cells carry α-1,3-galactose (α-Gal) glycans, and can bind to anti-Gal antibodies which are abundant in humans. The antibodies have protected humans and their ancestors for millions of years, because they inhibit replication of many kinds of microbes carrying αGal glycans and aid complements and macrophages to destroy them. Therefore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicating in nonprimate mammalian cells (eg, PK-15 cells) carry αGal glycans and could be employed as a live vaccine for corona virus 2019 (COVID-19). The live vaccine safety could be further enhanced through intramuscular inoculation to bypass the fragile lungs, like the live unattenuated adenovirus vaccine safely used in US recruits for decades. Moreover, the immune complexes of SARS-CoV-2 and anti-Gal antibodies could enhance the efficacy of COVID-19 vaccines, live or inactivated, carrying α-Gal glycans. Experiments are imperatively desired to examine these novel vaccine strategies which probably have the critical advantages for defeating the pandemic of COVID-19 and preventing other viral infectious diseases.

Live unattenuated vaccines for controlling viral diseases, including COVID-19.

Live unattenuated vaccines (LUVs) have been neglected for decades, due to widespread prejudice against their safety, even though they have successfully controlled yellow fever and adenovirus infection in humans as well as rinderpest and infectious bursal disease in animals. This review elucidated that LUVs could be highly safe with selective use of neutralizing antivirus antibodies, natural antiglycan antibodies, nonantibody antivirals, and ectopic inoculation. Also, LUVs could be of high efficacy, high development speed, and high production efficiency, with the development of humanized monoclonal antibodies and other modern technologies. They could circumvent antibody-dependent enhancement and maternal-derived antibody interference. With these important advantages, LUVs could be more powerful than other vaccines for controlling some viral diseases, and they warrant urgent investigation with animal experiments and clinical trials for defeating the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2.

Potential of live pathogen vaccines for defeating the COVID-19 pandemic: History and mechanism.

The whole world has entered a terrible crisis with a huge and increasing number of human deaths and economic losses in fighting the pandemic of COVID-19 caused by the novel coronavirus termed SARS-CoV-2. The live pathogen vaccine (LPV) strategy, which originated in ancient China for fighting smallpox, has been applied successfully by US military recruits for decades to control acute respiratory diseases caused by types 4 and 7 adenoviruses. This strategy has also been widely employed in veterinary medicine. These facts suggest a fast way out of the current pandemic crisis, namely that SARS-CoV-2 could be directly used as a live vaccine. Beyond the two traditional mechanisms to guarantee the LPV's safety (the LPV seed strain is properly selected; the LPV is inoculated bypassing the respiratory sites of pathology), three novel mechanisms to further ensure the LPV's safety are available (the virus replication is inhibited with early use of an antiviral drug; symptomatic LPV recipients are cured with convalescent plasma; the LPV is inoculated in the hot season). This LPV strategy has multiple potential advantages over other options and could reduce morbidity and mortality greatly as well as the economic loss caused by the pandemic. The safety and efficacy of this strategy should be investigated strictly using animal experiments and clinical trials, and even if the experiments and trials all support the strategy, it should be implemented with enough caution.

Potential for elimination of SAR-CoV-2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, future vaccination against COVID-19 may fall into long-term costly guerrilla warfare between SARS-CoV-2 and humans. Elimination of SARS-CoV-2 through vaccination to avoid the potential long-term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to the elimination of three human influenza viruses, which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggest that the rapid establishment of global herd immunity through mass vaccination using an appropriate vaccine could eliminate SARS-CoV-2. The coming 2 years are a golden time for elimination through vaccination, which requires tremendous national and international collaboration. This review also prioritizes the efficacy of vaccines for COVID-19 and elucidates the importance of the development of more live vaccines for COVID-19.

Decontamination of face masks with steam for mask reuse in fighting the pandemic COVID-19: Experimental supports.

The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.

Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2.

The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.

Subclinical highly pathogenic avian influenza virus infection among vaccinated chickens, China.

Subclinical infection of vaccinated chickens with a highly pathogenic avian influenza A(H5N2) virus was identified through routine surveillance in China. Investigation suggested that the virus has evolved into multiple genotypes. To better control transmission of the virus, we recommend a strengthened program of education, biosecurity, rapid diagnostics, surveillance, and elimination of infected poultry.

Identification of a potential novel type of influenza virus in Bovine in China.

Bovine influenza virus was first identified in the USA in 2013, and the virus represents a potential novel type of influenza viruses. However, the distribution and evolution of the virus remain unknown. We conducted a pilot survey of bovine influenza virus in China, and identified three bovine influenza viruses which are highly homogenous to the ones identified in the USA, suggesting that the bovine influenza virus likely circulates widely and evolves slowly in the world.

A clinical survey of common avian infectious diseases in China.

Multiple common avian infectious diseases (CAIDs), namely, avian infectious diseases excluding highly pathogenic avian influenza and Newcastle disease, such as avian salmonellosis and coccidiosis, cause huge economic loss in poultry production and are of great significance in public health. However, they are usually not covered in the systems for reporting of animal diseases. Consequently, the distribution of CAIDs is not clear in many countries. Here, we report a clinical survey of CAIDs in China based on clinical diagnosis of eight veterinary clinics in 2011 and 2012. This survey provided the distribution data of viral, bacterial, and parasitic CAIDs in different types of avian flocks, seasons, and regions, data that are of great value in the research, prevention, and control of poultry diseases. This survey suggested that avian colibacillosis, infectious serositis in ducks caused by Riemerella anatipestifer, avian salmonellosis, fowl cholera, avian mycoplasmosis, avian aspergillosis, coccidiosis, low pathogenic avian influenza, infectious bronchitis, infectious bursal disease, and infectious laryngotracheitis are likely to be prevalent in the poultry in China.

Viruses Identified in Shrews (Soricidae) and Their Biomedical Significance.

Shrews (Soricidae) are common small wild mammals. Some species of shrews, such as Asian house shrews (Suncus murinus), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including Adenoviridae, Arenaviridae, Arteriviridae, Astroviridae, Anelloviridae, Bornaviridae, Caliciviridae, Chuviridae, Coronaviridae, Filoviridae, Flaviviridae, Hantaviridae, Hepadnaviridae, Hepeviridae, Nairoviridae, Nodaviridae, Orthoherpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Phenuiviridae, Picobirnaviridae, Picornaviridae, Polyomaviridae, Poxviridae, Rhabdoviridae, Sedoreoviridae, Spinareoviridae, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses.

Development of a colloidal gold immunochromatographic strip for rapid detection of avian coronavirus infectious bronchitis virus.

Avian infectious bronchitis virus (IBV) still causes serious economic losses in the poultry industry. Currently, there are multiple prevalent genotypes and serotypes of IBVs. It is imperative to develop a new diagnosis method that is fast, sensitive, specific, simple, and broad-spectrum. A monoclonal hybridoma cell, N2D5, against the IBV N protein was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The N2D5 monoclonal antibody (mAb) and the previously prepared mouse polyclonal antibody against the IBV N protein were used to target IBV as a colloidal gold-mAb conjugate and a captured antibody, respectively, in order to develop an immunochromatographic strip. The optimal pH and minimum antibody concentration in the reaction system for colloidal gold-mAb N2D5 conjugation were pH 6.5 and 30 µg/mL, respectively. Common avian pathogens were tested to evaluate the specificity of the strip and no cross-reaction was observed. The sensitivity of the strip for detecting IBV was 10-1.4522 EID50/mL. The strip showed a broad-spectrum cross-reactive capacity for detecting IBV antigens, including multiple IBV genotypes in China and all of the seven serotypes of IBV that are currently prevalent in southern China. Additionally, the result can be observed within 2 min without any equipment. The throat and cloacal swab samples of chickens that were artificially infected with three IBV strains were tested using the developed strip and the qPCR method; the strip test demonstrated a high consistency in detecting IBV via qPCR gene detection. In conclusion, the immunochromatographic strip that was established is rapid, sensitive, specific, simple, practical, and broad-spectrum; additionally, it has the potential to serve as an on-site rapid detection method of IBV and can facilitate the surveillance and control of the disease, especially in resource-limited areas.

[Effect of continuous positive airway pressure on erectile dysfunction in patients with obstructive sleep apnea syndrome: a meta-analysis].

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) on erectile dysfunction (ED) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: We searched Cochrane Library, PubMed, China Academic Journal Full-Text Database, Chinese Biomedical Literature Database, Wanfang Resource Database and Chinese Journal Full-Text Database for clinical trials on the effect of CPAP on ED in OSAS patients. We identified the trials according to inclusion and exclusion criteria, evaluated their quality, and then extracted valid data for meta-analysis. RESULTS: We included 4 articles, 3 in English and 1 in Chinese, involving 77 cases of OSAS with ED. Meta-analysis revealed no statistically significant heterogeneity among different studies (P = 0.80; I2 = 0%), and therefore the fixed effect model was used for the analysis, which showed a significant increase in the IIEF-5 score after CPAP treatment (WMD = 4.19, 95% [3.01, 5.36], P < 0.001). CONCLUSION: The existing evidence from clinical trials shows that the CPAP therapy can significantly improve ED in OSAS patients. However, its efficacy has to be verified by randomized controlled clinical trials of higher quality and larger sample size.

Zoonotic Hantaviridae with Global Public Health Significance.

Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.