Mpox Virus and its Ocular Surface Manifestations.

The Mpox virus (MPXV) is the causative agent of human Mpox disease - a debilitating rash illness similar to smallpox. Although Clade I MPXV has remained endemic to West and Central Africa, Clade II MPXV has been responsible for many outbreaks worldwide. The most recent outbreak in 2022 resulted from the rapid spread of a new clade of MPXV, classified into Clade IIb - a distinct lineage from the previously circulating viral strains. The rapid spread and increased severity of Mpox disease by the Clade IIb strain have raised the serious public health imperative of better understanding the host and viral determinants during MPXV infection. In addition to typical skin rashes, including in the periorbital area, MPXV causes moderate to severe ophthalmic manifestations - most commonly, ocular surface complications (e.g., keratitis, conjunctivitis, blepharitis). While ocular manifestations of Clade I Mpox within the Congo basin have been well-reported, global incidence trends of ocular Mpox cases by Clade IIb are still emerging. Given the demonstrated ability of all MPXV strains to auto-inoculate ocular tissue alongside the enhanced transmissibility of the Clade IIb virus, there is an urgent need to elucidate the mechanisms by which MPXV causes ocular anomalies. In this review, we discuss the viral and genomic structures of MPXV, the epidemiology, and pathology of systemic and ocular Mpox, as well as potential prophylactic and therapeutic interventions.

The longevity response to warm temperature is neurally controlled via the regulation of collagen genes.

Studies in diverse species have associated higher temperatures with shorter lifespan and lower temperatures with longer lifespan. These inverse effects of temperature on longevity are traditionally explained using the rate of living theory, which posits that higher temperatures increase chemical reaction rates, thus speeding up the aging process. Recent studies have identified specific molecules and cells that affect the longevity response to temperature, indicating that this response is regulated, not simply thermodynamic. Here, we demonstrate that in Caenorhabditis elegans, functional loss of NPR-8, a G protein-coupled receptor related to mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C, and that the lifespan extension at 25°C is regulated by the NPR-8-expressing AWB and AWC chemosensory neurons as well as AFD thermosensory neurons. Integrative transcriptomic analyses revealed that both warm temperature and old age profoundly alter gene expression and that genes involved in the metabolic and biosynthetic processes increase expression at 25°C relative to 20°C, indicating elevated metabolism at warm temperature. These data demonstrate that the temperature-induced longevity response is neurally regulated and also provide a partial molecular basis for the rate of living theory, suggesting that these two views are not mutually exclusive. Genetic manipulation and functional assays further uncovered that the NPR-8-dependent longevity response to warm temperature is achieved by regulating the expression of a subset of collagen genes. As increased collagen expression is a common feature of many lifespan-extending interventions and enhanced stress resistance, collagen expression could be critical for healthy aging.

Novel approaches on identification of conserved miRNAs for broad-spectrum Potyvirus control measures.

Potyviridae comprises more than 200 ssRNA viruses, many of which have a broad host range and geographical distributions. Potyvirids (members of Potyviridae) infect several economically important plants such as saffron, cardamom, cucumber, pepper, potato, tomato, yam, etc. Cumulatively, potyvirids cause a substantial economic loss. The major bottleneck in developing an efficient antiviral strategy is that viruses quickly evade host immunity owing to their higher mutation and recombination rates. Due to this reason, the emergence of newer and improved broad-spectrum approaches to combat viral infections is essential. The use of microRNA's (miRNA) to circumvent viral infection against animal viruses has been successfully employed. Fewer studies reported the development of efficient miRNA-based antivirus resistant strategies against plant viruses and none focused on multiple virus resistance. We focused on potyviruses since studies are limited and identification of conserved miRNAs among various host plants would be an initiative to design broad-spectrum antivirus strategies. In this study, we predicted evolutionarily conserved miRNAs by BLAST searching of reported miRNAs from 15 plants against the GSS and EST sequences of banana. A total of nine miRNAs were predicted and screened in nine diverse potyvirids' hosts (Banana, Tomato, Green gram, Jasmine, Chilli, Coriander, Onion, Rose and Colocasia) belonging to eight different orders (Zingiberales, Solanales, Fabales, Lamiales, Apiales, Asperagales, Rosales and Alismatales). Results suggested that miR168 and miR162 are conserved among all the selected plants. This comprehensive study laid the foundations to design broad-spectrum antivirus resistance using miRNAs. To conclude miR168 and miR162 are conserved among many plants and play a crucial role in evading virus infection which could be used as a potential candidate for developing antiviral strategies against potyvirid infections.

Comparative study of potyvirid NIa proteases and their cleavage sites.

Nuclear inclusion a protease (NIaPro), a major protease of potyvirids, processes its cognate viral polyprotein at distinct cleavage sites. Although Potyviridae is the largest family of the realm Riboviria, the individual NIaPro enzymes and their cleavage sites are believed to be species-specific. In the present study, the NIaPro amino acid sequences of 165 potyvirids of 10 genera and their 1154 cleavage sites were compared to understand their genus/species-specificity and functional regulation. Of these, the NIaPro of macluraviruses, maintains a constant length of 217 amino acids, while those of other genera allow variation. In particular, poaceviruses exhibited a broad range of NIaPro amino acid sequence lengths. Alignment of 162 NIaPro amino acid sequences showed that the N- and C-terminal regions allow variations, while the central region, with the catalytic triad and S1 subsite, are highly conserved. NIaPro cleavage sites are composed of seven amino acids (heptapeptide) denoted as P6-P5-P4-P3-P2-P1/P1'. A survey of 1154 cleavage sites showed that the P1 position is predominantly occupied by Gln/Glu, as is seen in picornaviruses. The P6 (Glu), P4 (Val/Cys/Gln), P2 (His/Tyr/Leu), and P1' (Ser/Ala/Gly/Met) positions are predominantly occupied by genus-specific residues, while P5 and P3 are not genus-specific. The 6K2-VPg and VPg-NIaPro junctions possess Glu at the P1 position in order to maintain latency.

Novel interactions of cardamom mosaic virus VPg with cardamom histones H3 and H4.

The host genome targeting potyviral proteins is sparsely reported. Viral genome-linked protein (VPg) is a multifaceted protein known for its interactions with a suite of host proteins, guides essential viral life cycle processes such as genome replication, translation, genome packing, and antiviral defence. Besides, VPg also plays a crucial role in assisting the transport of nuclear inclusion a protease (NIa protease) into the host nucleus. Apart from that, the role of VPg in the nucleus of the cognate host is not clear. Although NIa protease has been reported for DNase activity, the molecular mechanisms underlying host genome accessibility are not yet understood completely. Here, we employed yeast two hybrid assays to test the cardamom histones H3 and H4 interaction with the VPg and NIa protease of macluravirus cardamom mosaic virus (CdMV). Although CdMV NIa protease has the putative histone-binding ER motif of MYST histone acetyltransferase, it did not interact with host histones H3 and H4. Surprisingly, CdMV VPg displayed strong interaction with histone proteins H3 and H4. Leucine prototrophy and ß-galactosidase assays were performed which validated VPg interaction with histones. To the best of our knowledge, this study is the first report for the multipartnered potyvirid protein VPg interaction with host histones H3 and H4.

Identification and characterization of virulent Aeromonas hydrophila Ah17 from infected Channa striata in river Cauvery and in vitro evaluation of shrimp chitosan.

Aeromonas hydrophila, an inhabitant in the aquatic ecosystem is considered as an important foodborne bacterial zoonotic pathogen in aquaculture. The present study aimed to identify virulent A. hydrophila from naturally infected Channa striata in river Cauvery and in vitro evaluation of shrimp chitosan. Rimler Shotts (RS) and blood agar medium identified the presence of pathogenic Aeromonas sp. from the infected C. striata. A. hydrophila Ah17 was identified using 16S rRNA nucleotide sequence. Extracellular enzymes such as amylase, lipase, and protease were screened in A. hydrophila Ah17. Antibiotic susceptibility tests showed A. hydrophila Ah17 was highly resistant against ß-lactam, glycopeptide, macrolides, phosphonic, fucidin, and oxazolidinone classes of antibiotics. Virulent genes such as hemolysin (aer and hly), heat-labile enterotoxin (act), cytotonic heat-stable enterotoxin (ast), elastase (ahyB), and lipase (lip) were identified. Growth and the viable cell population of virulent A. hydrophila Ah17 were significantly reduced in a dose-dependent manner against shrimp chitosan (CHS) from Penaeus indicus (P. indicus). Thus, the present study isolated virulent A. hydrophila Ah17 from the environmental source and characterized in vitro with shrimp chitosan.

Hubei poty-like virus 1 is likely an interspecies recombinant of sugarcane mosaic virus and putative bean yellow mosaic virus.

In 2016, Shi et al. (Nature 540:539-543. https://doi.org/10.1038/nature20167 2016) reported Hubei poty-like virus 1 (HuPLV1) to be a new member of the family Potyviridae. At that time, its polyprotein shared the highest sequence identity (80%) with sugarcane mosaic virus (SCMV). A year later, two isolates of SCMV from Canna sp. whose sequences were submitted to the GenBank database showed 91% identity to the HuPLV1 polyprotein sequence. Based on the species demarcation criteria for the family Potyviridae, HuPLV1 should possibly be considered an isolate of SCMV. To resolve this taxonomical inconsistency, we carried out a phylogenetic and recombination analysis and found that HuPLV1 is an interspecies recombinant of SCMV and bean yellow mosaic virus (BYMV).

Wuhan poty-like virus 1 is a possible member of the genus Macluravirus.

We have analysed the genome sequence of Wuhan poty-like virus 1 (WuPLV1), reported as an unclassified RNA virus in GenBank (Accession no: KX884573.1). Based on the polyprotein sequence identity (ranging from 55.2 to 71.1%), with classifiable members of the Macluravirus genus of the plant virus family Potyviridae, we suggest that WuPLV1 represents a possible new species of Macluravirus, although the virus was isolated from the Chinese land snail Mastigeulota kiangsinensis, which is not known to be a host or vector of macluraviruses.

Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback regulation.

Streptomyces peucetius self-resistance genes drrA and drrB encode membrane-associated proteins that function like an ABC transporter for the efflux of daunorubicin and to maintain a constant subinhibitory physiological concentration of the drug within the cell. In this study, the drrA and drrB operons were disrupted for investigating drug production, self-resistance and regulation. The drrA-drrB null mutant was highly sensitive to daunorubicin. A 10-fold decrease in drug production was observed in the null mutant compared with the wild-type strain. We propose that the absence of a drug-specific efflux pump increases the intracellular concentration of daunorubicin, which is sensed by the organism to turn down drug production. Quantitative real-time PCR analysis of the mutant showed a drastic reduction in the expression of the key regulator dnrI and polyketide synthase gene dpsA. However, the expression of regulatory genes dnrO and dnrN was increased. Feedback regulation based on the intracellular daunorubicin concentration is discussed.