A world of viruses nested within parasites: Unraveling viral diversity within parasitic flatworms (Platyhelminthes)

Because parasites have an inextricable relationship with their host, they have the potential to serve as viral reservoirs or facilitate virus host-shifts. Yet, little is known about viruses infecting parasitic hosts except for blood-feeding arthropods that are well-known vectors of zoonotic viruses. Herein we uncover viruses of flatworms (Phylum Platyhelminthes, group Neodermata) that specialize in parasitizing vertebrates and their ancestral free-living relatives. We discovered 115 novel viral sequences, including 1 in Macrostomorpha, 5 in Polycladida, 44 in Tricladida, 1 in Monogenea, 15 in Cestoda and 49 in Trematoda, through data mining. The majority of newly identified viruses constitute novel families or genera. Phylogenetic analyses show that the virome of flatworms changed dramatically during the transition of Neodermatans to a parasitic lifestyle. Most Neodermatan viruses seem to co-diversify with their host , with the exception of rhabdoviruses which may switch host more often, based on phylogenetic relationships. Neodermatan rhabodviruses also have an ancestral position to vertebrate-associated viruses, including Lyssaviruses, suggesting that vertebrate rhabdoviruses emerged from a flatworm rhabdovirus in a parasitized host. This study reveals an extensive diversity of viruses in Platyhelminthes and highlights the need to evaluate the role of viral infection in flatworm-associated diseases.

Reprogrammed Pteropus Bat Stem Cells as A Model to Study Host-Pathogen Interaction during Henipavirus Infection

Bats are natural hosts for numerous zoonotic viruses, including henipaviruses, which are highly pathogenic for humans, livestock, and other mammals but do not induce clinical disease in bats. Pteropus bats are identified as a reservoir of henipaviruses and the source of transmission of the infection to humans over the past 20 years. A better understanding of the molecular and cellular mechanisms allowing bats to control viral infections requires the development of relevant, stable, and permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a combination of ESRRB (Estrogen Related Receptor Beta), CDX2 (Caudal type Homeobox 2), and c-MYC (MYC proto-oncogene) transcription factors, we generated bat reprogrammed cells. These cells exhibit stem cell-like characteristics and neural stem cell molecular signature. In contrast to primary fibroblastic cells, these reprogrammed stem cells are highly permissive to henipaviruses and exhibit specific transcriptomic profiles with the particular expression of certain susceptibility factors such as interferon-stimulated genes (ISG), which may be related to viral infection. These Pteropus bat reprogrammed stem cells should represent an important experimental tool to decipher interactions during henipaviruses infection in Pteropus bats, facilitate isolation and production of bat-borne viruses, and to better understand the bat biology.

SARS-CoV-2 Therapeutic Landscape, Opportunity and Future Threats

During the past two decades, the world has seen several known and novel zoonotic viruses and deadly bacterial diseases, such as West Nile Virus (1999 to 2002), Anthrax (2001), H1N1(2009), Ebola (2014), Zika Virus (2016), SARS-CoV (2002), MERS-CoV (2012) and SARS-CoV-2 in 2019. The current ongoing COVID-19 pandemic is completely unpredicted and it has hugely changed our health care systems, global economy and social lifestyles. SARS-CoV-2 is still under genetic evolution and getting mutated to escape our immune system and showing resistance against available therapies. In this current research work, we have examined all publicly available scientific literature to date to understand the genetic evaluation of coronavirus species and their transmission possibilities to humans. We have also explored recently reported mutations of concerns in viral spike glycoprotein. We then discussed various SARS-CoV-2 preclinical and clinical research breakthroughs and highlighted our limitations and readiness to combat this deadly disease. Based on our recent study, we have emphasized developing a global viral, fungi and microbes platform. It can help us to predict mutations on their genomic, structural and pathophysiological profile to better address early on future threats by such infectious agents.

Hepatitis E Virus (HEV) in Imported and Domestic Camels in Saudi Arabia – A Cross-Sectional Descriptive Molecular Study

Camels gained attention since the discovery of MERS-CoV as intermediary hosts for potentially epidemic zoonotic viruses. DcHEV is a novel zoonotic pathogen associated with camel contact. This study aimed to genetically characterize DcHEV in domestic and imported camels in Saudi Arabia. DcHEV was detected by RT-PCR in serum samples, PCR-positive samples were subjected to sequencing and phylogenetic analyses. DcHEV was detected in 1.77% of samples with higher positivity in domestic DCs. All positive imported dromedaries were from Sudan with age declining prevalence. Domestic DcHEV sequences clustered with sequences from Kenya, Somalia, and UAE while imported sequences clustered with one DcHEV isolate from UAE and both sequences clustered away from isolates reported from Pakistan. Full-genome sequences showed 24 amino acid difference with reference sequences. Our results confirm the detection of DcHEV in domestic and imported DCs. Further investigations are needed in human and camel populations to identify DcHEV potential zoonosis threat.

Ecology of Powassan Virus in the United States

Zoonotic viruses threaten the lives of millions of people annually, exacerbated by climate change, human encroachment into wildlife habitats, and habitat destruction. The Powassan virus (POWV) is a rare tick-borne virus that can cause severe neurological damage and death, and the incidence of the associated disease (Powassan virus disease) is increasing in the eastern United States. The mechanisms by which POWV is maintained in nature and transmitted to humans are complex and only partly understood. This review provides an overview of what is known about the vector species, vector-host transmission dynamics, and environmental and human-driven factors that may be aiding the spread of both the vector and virus.

Biosynthesis of α-Gal Epitopes (Galα1-3Galβ1-4GlcNAc-R) and Their Unique Potential in Future α-Gal Therapies

The α-gal epitope is a carbohydrate antigen which appeared early in mammalian evolution and is synthesized in large amounts by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT) in non-primate mammals, lemurs, and New-World monkeys. Ancestral Old-World monkeys and apes synthesizing α-gal epitopes underwent complete extinction 20–30 million years ago, and their mutated progeny lacking α-gal epitopes survived. Humans, apes, and Old-World monkeys which evolved from the surviving progeny lack α-gal epitopes and produce the natural anti-Gal antibody which binds specifically to α-gal epitopes. Because of this reciprocal distribution of the α-gal epitope and anti-Gal in mammals, transplantation of organs from non-primate mammals (e.g., pig xenografts) into Old-World monkeys or humans results in hyperacute rejection following anti-Gal binding to α-gal epitopes on xenograft cells. The in vivo immunocomplexing between anti-Gal and α-gal epitopes on molecules, pathogens, cells, or nanoparticles may be harnessed for development of novel immunotherapies (referred to as “α-gal therapies”) in various clinical settings because such immune complexes induce several beneficial immune processes. These immune processes include localized activation of the complement system which can destroy pathogens and generate chemotactic peptides that recruit antigen-presenting cells (APCs) such as macrophages and dendritic cells, targeting of antigens presenting α-gal epitopes for extensive uptake by APCs, and activation of recruited macrophages into pro-reparative macrophages. Some of the suggested α-gal therapies associated with these immune processes are as follows: 1. Increasing efficacy of enveloped-virus vaccines by synthesizing α-gal epitopes on vaccinating inactivated viruses, thereby targeting them for extensive uptake by APCs. 2. Conversion of autologous tumors into antitumor vaccines by expression of α-gal epitopes on tumor cell membranes. 3. Accelerating healing of external and internal injuries by α-gal nanoparticles which decrease the healing time and diminish scar formation. 4. Increasing anti-Gal–mediated protection against zoonotic viruses presenting α-gal epitopes and against protozoa, such as Trypanosoma, Leishmania, and Plasmodium, by vaccination for elevating production of the anti-Gal antibody. The efficacy and safety of these therapies were demonstrated in transgenic mice and pigs lacking α-gal epitopes and producing anti-Gal, raising the possibility that these α-gal therapies may be considered for further evaluation in clinical trials.

Reservoir host immunology and life history shape virulence evolution in zoonotic viruses

Future pandemic risk management requires better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, suggesting that reservoir host immunological and life history traits may be important drivers of cross-species virulence. Using a nested population-level and within-host modelling approach, we generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, successfully recapturing corresponding virus-induced human mortality rates from the literature. Our work offers a mechanistic explanation for the virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, tolerance, and population density impact the evolution of viral traits that generate severe disease following spillover to humans. We provide a theoretical framework that offers a series of testable questions and hypotheses designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts.

Incursion of European Bat Lyssavirus 1 (EBLV-1) in Serotine Bats in the United Kingdom

Lyssaviruses are an important genus of zoonotic viruses which cause the disease rabies. The United Kingdom is free of classical rabies (RABV). However, bat rabies due to European bat lyssavirus 2 (EBLV-2), has been detected in Daubenton’s bats (Myotis daubentonii) in Great Britain since 1996, including a fatal human case in Scotland in 2002. Across Europe, European bat lyssavirus 1 (EBLV-1) is commonly associated with serotine bats (Eptesicus serotinus). Despite the presence of serotine bats across large parts of southern England, EBLV-1 had not previously been detected in this population. However, in 2018, EBLV-1 was detected through passive surveillance in a serotine bat from Dorset, England, using a combination of fluorescent antibody test, reverse transcription-PCR, Sanger sequencing and immunohistochemical analysis. Subsequent EBLV-1 positive serotine bats have been identified in South West England, again through passive surveillance, during 2018, 2019 and 2020. Here, we confirm details of seven cases of EBLV-1 and present similarities in genetic sequence indicating that emergence of EBLV-1 is likely to be recent, potentially associated with the natural movement of bats from the near continent

TR Locus Annotation and Characteristics of Rhinolophus ferrumequinum

T-cell antigen receptors (TRs) in vertebrates can be divided into αβ or γδ, encoded by TRA/D, TRG, or TRB loci. TRs play a central role in mammal cellular immunity, which occurs by rearrangement of V, D, J, and C genes in the loci. The bat is the only mammal with flying ability and is considered the main host of zoonotic viruses, an important public health concern. However, at present, little is known about the composition of bat TR genes. Based on the whole genome sequence of the greater horseshoe bat (Rhinolophus ferrumequinum) and referring to the TR/IG annotation rules formulated by the international ImMunoGeneTics information system (IMGT), we present a complete annotation of TRA/D, TRG, and TRB loci of R. ferrumequinum. A total of 128 V segments, three D segments, 85 J segments, and 6 C segments were annotated and compared with other known mammalian data. The characteristics of the TR locus and germline genes of R. ferrumequinum are analyzed.