The Impact of Drugs and Substance Abuse on Viral Pathogenesis-A South African Perspective.

Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.

Zoonotic spillover and extreme weather events drive the global outbreaks of airborne viral emerging infectious diseases.

Outbreaks of airborne viral emerging infectious diseases (EIDs) cause an increasing burden on global public health, particularly with a backdrop of intensified climate change. However, infection sources and drivers for outbreaks of airborne viral EIDs remain unknown. Here, we aim to explore the driving mechanisms of outbreaks based on the one health perspective. Outbreak information for 20 types of airborne viral EIDs was collected from the Global Infectious Disease and Epidemiology Network database and a systematic literature review. Four statistically significant and high-risk spatiotemporal clusters for airborne viral EID outbreaks were identified globally using multivariate scan statistic tests. There were 112 outbreaks with clear infection sources, and zoonotic spillover was the most common source (95.54%, 107/112). Since 1970, the majority of outbreaks occurred in healthcare facilities (24.82%), followed by schools (17.93%) and animal-related settings (15.93%). Significant associations were detected between the number of earthquakes, storms, duration of floods, and airborne viral EIDs' outbreaks using a case-crossover study design and multivariable conditional logistic regression. These findings implied that zoonotic spillover and extreme weather events are driving global outbreaks of airborne viral EIDs, and targeted prevention and control measures should be made to reduce the airborne viral EIDs burden.

Diversity, evolution, and emergence of fish viruses.

The production of aquatic animals has more than doubled over the last 50 years and is anticipated to continually increase. While fish are recognized as a valuable and sustainable source of nutrition, particularly in the context of human population growth and climate change, the rapid expansion of aquaculture coincides with the emergence of highly pathogenic viruses that often spread globally through aquacultural practices. Here, we provide an overview of the fish virome and its relevance for disease emergence, with a focus on the insights gained through metagenomic sequencing, noting potential areas for future study. In particular, we describe the diversity and evolution of fish viruses, for which the majority have no known disease associations, and demonstrate how viruses emerge in fish populations, most notably at an expanding domestic-wild interface. We also show how wild fish are a powerful and tractable model system to study virus ecology and evolution more broadly and can be used to identify the major factors that shape vertebrate viromes. Central to this is a process of virus-host co-divergence that proceeds over many millions of years, combined with ongoing cross-species virus transmission.

Susceptibility of solid organ transplant recipients to viral pathogens with zoonotic potential: A mini-review.

A substantial number of zoonotic diseases are caused by viral pathogens, representing a significant menace to public health, particularly to susceptible populations, such as pregnant women, the elderly, and immunocompromised individuals. Individuals who have undergone solid organ transplantation frequently experience immunosuppression, to prevent organ rejection, and, thus are more prone to opportunistic infections. Furthermore, the reactivation of dormant viruses can threaten transplant recipients and organ viability. This mini-review examines the up-to-date literature covering potential zoonotic and organ rejection-relevant viruses in solid organ transplant recipients. A comprehensive list of viruses with zoonotic potential is highlighted and the most important clinical outcomes in patients undergoing transplantation are described. Moreover, this mini-review calls attention to complex multifactorial events predisposing viral coinfections and the need for continuous health surveillance and research to understand better viral pathogens' transmission and pathophysiology dynamics in transplanted individuals.

Pathogenesis of viral infections during pregnancy.

SUMMARYViral infections during pregnancy are associated with significant adverse perinatal and fetal outcomes. Pregnancy is a unique immunologic and physiologic state, which can influence control of virus replication, severity of disease, and vertical transmission. The placenta is the organ of the maternal-fetal interface and provides defense against microbial infection while supporting the semi-allogeneic fetus via tolerogenic immune responses. Some viruses, such as cytomegalovirus, Zika virus, and rubella virus, can breach these defenses, directly infecting the fetus and having long-lasting consequences. Even without direct placental infection, other viruses, including respiratory viruses like influenza viruses and severe acute respiratory syndrome coronavirus 2, still cause placental damage and inflammation. Concentrations of progesterone and estrogens rise during pregnancy and contribute to immunological adaptations, placentation, and placental development and play a pivotal role in creating a tolerogenic environment at the maternal-fetal interface. Animal models, including mice, nonhuman primates, rabbits, and guinea pigs, are instrumental for mechanistic insights into the pathogenesis of viral infections during pregnancy and identification of targetable treatments to improve health outcomes of pregnant individuals and offspring.

A Numerical Investigation into the Spread Characteristics of a Human Virus-Carrying Droplet in a Classroom Environment.

In public health, the transmission characteristics and laws of highly infectious virus-carrying particles in the air environment have become a hot topic. The study on the spread characteristics of human virus-carrying droplets in a typical densely populated space is necessary. As such, a classroom space lattice Boltzmann method (LBM) model with a dense population is established to simulate and analyze the spreading and diffusing behavior of pathogenic droplets. The results show that the dispersion density is mainly affected by the mainstream wind direction in the area of concern, and particle aggregation is more likely to form in the area close to the wind disturbance. Due to the dense thermal plumes, the droplet movement is a clear convergence towards the upper space of the classroom. This could explain the fact that people living above confirmed cases are now more likely to be infected.

Assessing suspension and infectivity times of virus-loaded aerosols involved in airborne transmission.

Airborne transmission occurs through droplet-mediated transport of viruses following the expulsion of an aerosol by an infected host. Transmission efficiency results from the interplay between virus survival in the drying droplet and droplet suspension time in the air, controlled by the coupling between water evaporation and droplet sedimentation. Furthermore, droplets are made of a respiratory fluid and thus, display a complex composition consisting of water and nonvolatile solutes. Here, we quantify the impact of this complex composition on the different phenomena underlying transmission. Solutes lead to a nonideal thermodynamic behavior, which sets an equilibrium droplet size that is independent of relative humidity. In contrast, solutes do not significantly hinder transport due to their low initial concentration. Realistic suspension times are computed and increase with increasing relative humidity or decreasing temperature. By uncoupling drying and suspended stages, we observe that enveloped viruses may remain infectious for hours in dried droplets. However, their infectivity decreases with increasing relative humidity or temperature after dozens of minutes. Examining expelled droplet size distributions in the light of these results leads to distinguishing two aerosols. Most droplets measure between 0 and 40 µm and compose an aerosol that remains suspended for hours. Its transmission efficiency is controlled by infectivity, which decreases with increasing humidity and temperature. Larger droplets form an aerosol that only remains suspended for minutes but corresponds to a much larger volume and thus, viral load. Its transmission efficiency is controlled by droplet suspension time, which decreases with increasing humidity and decreasing temperature.

Mosquito saliva enhances virus infection through sialokinin-dependent vascular leakage.

Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of heterogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes-mosquito-borne viruses.

Enteric viruses replicate in salivary glands and infect through saliva.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

COVID-19-lessons for zoonotic disease.

Disease emergence is driven by human-animal contact in a global viral ecosystem.

Honey bees and climate explain viral prevalence in wild bee communities on a continental scale.

Viruses are omnipresent, yet the knowledge on drivers of viral prevalence in wild host populations is often limited. Biotic factors, such as sympatric managed host species, as well as abiotic factors, such as climatic variables, are likely to impact viral prevalence. Managed and wild bees, which harbor several multi-host viruses with a mostly fecal-oral between-species transmission route, provide an excellent system with which to test for the impact of biotic and abiotic factors on viral prevalence in wild host populations. Here we show on a continental scale that the prevalence of three broad host viruses: the AKI-complex (Acute bee paralysis virus, Kashmir bee virus and Israeli acute paralysis virus), Deformed wing virus, and Slow bee paralysis virus in wild bee populations (bumble bees and solitary bees) is positively related to viral prevalence of sympatric honey bees as well as being impacted by climatic variables. The former highlights the need for good beekeeping practices, including Varroa destructor management to reduce honey bee viral infection and hive placement. Furthermore, we found that viral prevalence in wild bees is at its lowest at the extreme ends of both temperature and precipitation ranges. Under predicted climate change, the frequency of extremes in precipitation and temperature will continue to increase and may hence impact viral prevalence in wild bee communities.

Novel viruses highlight risks of Asia's wild animal trade.

Sampling of game in China reveals many viral threats.

Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions.

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host-pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.

Natural rodent model of viral transmission reveals biological features of virus population dynamics.

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.

ZOVER: the database of zoonotic and vector-borne viruses.

Emerging infectious diseases significantly threaten global public health and socioeconomic security. The majority of emerging infectious disease outbreaks are caused by zoonotic/vector-borne viruses. Bats and rodents are the two most important reservoir hosts of many zoonotic viruses that can cross species barriers to infect humans, whereas mosquitos and ticks are well-established major vectors of many arboviral diseases. Moreover, some emerging zoonotic diseases require a vector to spread or are intrinsically vector-borne and zoonotically transmitted. In this study, we present a newly upgraded database of zoonotic and vector-borne viruses designated ZOVER (http://www.mgc.ac.cn/ZOVER). It incorporates two previously released databases, DBatVir and DRodVir, for bat- and rodent-associated viruses, respectively, and further collects up-to-date knowledge on mosquito- and tick-associated viruses to establish a comprehensive online resource for zoonotic and vector-borne viruses. Additionally, it integrates a set of online visualization tools for convenient comparative analyses to facilitate the discovery of potential patterns of virome diversity and ecological characteristics between/within different viral hosts/vectors. The ZOVER database will be a valuable resource for virologists, zoologists and epidemiologists to better understand the diversity and dynamics of zoonotic and vector-borne viruses and conduct effective surveillance to monitor potential interspecies spillover for efficient prevention and control of future emerging zoonotic diseases.

VThunter: a database for single-cell screening of virus target cells in the animal kingdom.

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.

Healthcare worker protection against epidemic viral respiratory disease.

Lower respiratory infections are often caused or precipitated by viruses and are a leading cause of global morbidity and mortality. Mutations in these viral genomes can produce highly infectious strains that transmit across species and have the potential to initiate epidemic, or pandemic, human viral respiratory disease. Transmission between humans primarily occurs via the airborne route and is accelerated by our increasingly interconnected and globalised society. To this date, there have been four major human viral respiratory outbreaks in the 21st century. Healthcare workers (HCWs) are at particular risk during respiratory epidemics or pandemics. This is due to crowded working environments where social distancing, or wearing respiratory personal protective equipment for prolonged periods, might prove difficult, or performing medical procedures that increase exposure to virus-laden aerosols, or bodily fluids. This review aims to summarise the evidence and approaches to occupational risk and protection of HCWs during epidemic or pandemic respiratory viral disease.