Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Molecular Virology of Orthopoxviruses with Special Reference to Monkeypox Virus.

Poxviruses are large (200-450 nm) and enveloped viruses carrying double-stranded DNA genome with an epidermal cell-specific adaptation. The genus Orthopoxvirus within Poxviridae family constitutes several medically and veterinary important viruses including variola (smallpox), vaccinia, monkeypox virus (MPXV), and cowpox. The monkeypox disease (mpox) has recently emerged as a public health emergency caused by MPXV. An increasing number of human cases of MPXV have been documented in non-endemic nations without any known history of contact with animals brought in from endemic and enzootic regions, nor have they involved travel to an area where the virus was typically prevalent. Here, we review the MPXV replication, virus pathobiology, mechanism of viral infection transmission, virus evasion the host innate immunity and antiviral therapies against Mpox. Moreover, preventive measures including vaccination were discussed and concluded that cross-protection against MPXV may be possible using antibodies that are directed against an Orthopoxvirus. Despite the lack of a specialised antiviral medication, several compounds such as Cidofovir and Ribavirin warrant consideration against mpox.

Potential reverse spillover of infectious bursal disease virus at the interface of commercial poultry and wild birds.

Recently, multiple spillover events between domesticated poultry and wild birds have been reported for several avian viruses. This phenomenon highlights the importance of the livestock-wildlife interface in the possible emergence of novel viruses. The aim of the current study was to investigate the potential spillover and epidemiological links of infectious bursal disease virus (IBDV) between wild birds and domestic poultry. To this end, twenty-eight cloacal swabs were collected from four species of free-living Egyptian wild birds (i.e. mallard duck, bean goose, white-fronted goose and black-billed magpie). Genetic and phylogenetic analysis of three positive isolates revealed that the IBDV/USC-1/2019 strain clustered with previously reported very virulent IBDV (vvIBDV) Egyptian isolates. Interestingly, two other wild bird-origin isolates (i.e. IBDV/USC-2/2019 and IBDV/USC-3/2019) grouped with a vaccine strain that is being used in commercial poultry. In conclusion, our results revealed the molecular detection of vaccine and vvIBDV-like strains in Egyptian wild birds and highlighted the potential role of wild birds in IBDV epidemiology in disease-endemic regions.

Interferon-induced protein with tetratricopeptide repeats 5 of black fruit bat (Pteropus alecto) displays a broad inhibition of RNA viruses.

Bats are natural host reservoirs and have adapted a unique innate immune system that permits them to host many viruses without exhibiting symptoms. Notably, bat interferon stimulated genes (ISGs) have been shown to play antiviral roles. Interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is a well-characterised ISG in humans with antiviral activities against negative-sense RNA viruses via inhibiting viral transcription. Here, we aim to investigate if Pteropus alecto (pa) IFIT5 (paIFIT5) possess the ability to inhibit negative-sense RNA viruses. Initially, gene syntenic and comparative structural analyses of multiple animals highlighted a high level of similarity between Pteropus alecto and human IFIT5 proteins. Our results showed that paIFIT5 was significantly inducible by viral and dsRNA stimulation. Transient overexpression of paIFIT5 inhibited the replication of vesicular stomatitis virus (VSV). Using minireplicon and transcription reporter assays, we demonstrated the ability of paIFIT5 specifically to inhibit H17N10 polymerase activity. Mechanistically, we noticed that the antiviral potential of paIFIT5 against negative sense RNA viruses was retributed to its interaction with 5'ppp containing RNA. Taken together, these findings highlight the genetic and functional conservation of IFIT5 among mammals.

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity.

The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human agniotensin-converting enzyme 2 (hACE2) receptor. To this end, we have applied a string of deep structural and genetic analysis tools to map the substitution patterns in the S protein of major Omicron sub-variants (n = 51) with a primary focus on the RBD mutations. This head-to-head comparison of Omicron sub-variants revealed multiple simultaneous mutations that are attributed to antibody escape, and increased affinity and binding to hACE2. Our deep mapping of the substitution matrix indicated a high level of diversity at the N-terminal and RBD domains compared with other regions of the S protein, highlighting the importance of these two domains in a matched vaccination approach. Structural mapping identified highly variable mutations in the up confirmation of the S protein and at sites that critically define the function of the S protein in the virus pathobiology. These substitutional trends offer support in tracking mutations along the evolutionary trajectories of SAR-CoV-2. Collectively, the findings highlight critical areas of mutations across the major Omicron sub-variants and propose several hotspots in the S proteins of SARS-CoV-2 sub-variants to train the future design and development of COVID-19 vaccines.

Insights into the Genetic Evolution of Duck Hepatitis A Virus in Egypt.

Duck hepatitis virus (DHV) is one of the commercially important diseases of ducklings worldwide. It is an acute and highly infectious disease of ducklings caused by three different serotypes (1-3) of duck hepatitis A virus (DHAV), and serotype 1 is the most common in poultry. To date, little is known about the prevalence and genetic characterisation of DHAV-1 in Egypt. In the current study, isolation and complete genomic analyses of DHAVs circulating in commercial duck farms in different Egyptian governorates were conducted. A total of eighteen samples were collected from six Egyptian governorates of 3-11 days old ducklings (Pekin and Mullard) with a history of nervous signs and high mortality rates. Five out of eighteen (5/18) samples were screened positive for the DHAV-1 based on the VP1 gene. These samples were individually used for virus isolation in embryonated duck embryos (EDE), followed by complete genome sequencing. Phylogenomic analyses showed that DHAV serotype I; genotype I were diversified into four different groups (1-4). Most of the recent circulating Egyptian DHAV strains are clustered within group 4, while isolates characterised within this study were clustered within group 1. Recombination analyses revealed that the emergence of a new recombinant virus-DHAV-1 strain Egypt-10/2019-through recombination. Likewise, the selective pressure analyses showed the existence, inside or near areas of the viral attachment or related functions, of positive scores highlighting the importance of natural selection and viral evolution mechanism at different protein domains. The findings of this study provide updated information on the epidemiological and genetic features of DHAV-1 strains and underscore the importance of DHAV surveillance as well as re-evaluation for currently used vaccines.

Chickens Expressing IFIT5 Ameliorate Clinical Outcome and Pathology of Highly Pathogenic Avian Influenza and Velogenic Newcastle Disease Viruses.

Innate antiviral immunity establishes first line of defense against invading pathogens through sensing their molecular structures such as viral RNA. This antiviral potential of innate immunity is mainly attributed to a myriad of IFN-stimulated genes (ISGs). Amongst well-characterized ISGs, we have previously shown that antiviral potential of chicken IFN-induced proteins with tetratricopeptides repeats 5 (chIFIT5) is determined by its interaction potential with 5'ppp containing viral RNA. Here, we generated transgenic chickens using avian sarcoma-leukosis virus (RCAS)-based gene transfer system that constitutively and stably express chIFIT5. The transgenic chickens infected with clinical dose (EID50 104 for HPAIV and 105 EID50 for vNDV) of high pathogenicity avian influenza virus (HPAIV; H5N1) or velogenic strain of Newcastle disease virus (vNDV; Genotype VII) showed marked resistance against infections. While transgenic chickens failed to sustain a lethal dose of these viruses (EID50 105 for HPAIV and 106 EID50 for vNDV), a delayed and lower level of clinical disease and mortality, reduced virus shedding and tissue damage was observed compared to non-transgenic control chickens. These observations suggest that stable expression of chIFIT5 alone is potentially insufficient in providing sterile protection against these highly virulent viruses; however, it is sufficient to ameliorate the clinical outcome of these RNA viruses. These findings propose the potential of innate immune genes in conferring genetic resistance in chickens against highly pathogenic and zoonotic viral pathogens causing sever disease in both animals and humans.