hepatitis A vaccine (Havisure)

Comparative Sequence Analysis of the Envelope Gene of Kyasanur Forest Disease Virus Vaccine Strain With Currently Circulating Field Strains.

Kaje Keerthi K, Marinaik Chandranaik B CB, Gomes Amitha Reena AR, Rizwan Apsana A et al.

The present study was undertaken with the objective of performing comparative sequence analysis of the envelope (E) gene of Kyasanur forest disease virus (KFDV) vaccine strain P9605 with the circulating field strains. The study was taken up as the currently used KFDV vaccine strain, KFDV P9605, was isolated in the 1960s. For this study, we designed two sets of primers targeting the complete amplification of the E gene of KFDV. The sequencing was performed by the Sanger method, and the deduced sequence of the vaccine virus was deposited in GenBank with accession number PX067005. This sequence obtained for the vaccine virus was aligned and compared with sequences of GenBank-deposited circulating field strains. We also performed comparative sequence analysis of the Kyasanur forest disease (KFD) vaccine seed virus having passaged twice in mouse brain with the vaccine seed virus passaged six times in mouse brain to investigate whether multiple passages in mouse brain will lead to genetic mutation in the immunologically important E gene. The phylogenetic analysis revealed seven amino acid mutations in the field strains at positions A123T, S158N, D178E, D239N, A313S, M429I, and G479A when compared with the vaccine strain. We did not find any mutations at the critical fusogenic segment (residues 98-113) in the E gene of currently circulating field strains compared to the vaccine seed virus. The study found no genetic variations in the E gene of the KFD virus passed two times and passed six times in mouse brain. We performed SWISS-MODEL homology modeling, AlphaFold protein analysis, and Ramachandran plot analysis to study the E protein structures and stability. The observations made in this study suggest slow evolutionary drift and conserved structural stability of the envelope gene of KFDV ever since its emergence 7 decades ago; however, the functional implications of these amino acid substitutions need further studies on their roles in viral infectivity, transmission, and impact on immunity.

Regulatory roles of G-quadruplexes and G-quadruplex-binding proteins across the enhancer and promoter of the HBV genome.

He Lina L, Huang Baoyue B, Ma Haiyang H, Wang Lin L et al.

Hepatitis B virus (HBV) infection poses a global threat to human health due to the limited availability of effective treatment options. Recent studies have shown that the structures of G-quadruplex (G4) are related to the pathogenesis of the virus and potential targets for antiviral therapy. G-quadruplex-binding proteins (G4BPs) play a key role in regulating the G4 landscape and its associated functions by anchoring, stabilizing, or unwinding G4 structures. Researchers have actively pursued the identification of G4 structures within the HBV genome, yet a comprehensive, genome-wide analysis revealing their regulatory role and that of G4BPs has remained largely elusive. Consequently, our understanding of the intricate interactions between HBV G4 and G4BPs remains quite limited. Biophysical and molecular biology approaches were employed to investigate HBV G4, focusing on core promoter and enhancer (CP/EN) activities. Mass spectrometry, DNA pull-down, and surface plasmon resonance (SPR) characterized interactions between G4 and G4BPs. Employing the dual luciferase reporter system and HBV infection model, this study utilized binding assays designed for the G4 mutant, alongside overexpression and knockdown experiments, to delve into the regulatory functions of G4 and G4BPs. We identified two functional G4 elements located at positions 1204 and 1732 within the HBV CP/EN regulatory region. Reporter assays containing the CP/EN sequences showed that disruption of either the 1204 or 1732 G4 structure significantly reduced promoter activity. In the HBV 1.3-mer system, disruption of the 1732 G4 markedly decreased HBsAg, HBeAg and HBcAg expression, whereas total HBV RNA and 3.5 kb RNA levels were not significantly affected. Both G4 elements selectively recruited multiple host proteins in vitro, among which the 1732 displayed stronger binding to HNF4A. Functional assays further demonstrated that HNF4A enhanced CP/EN-driven reporter activity in a G4-dependent manner, and stabilization of G4 structures by BRACO-19 further promoted the interaction between G4 and HNF4A. In addition, CNBP, the most highly enriched G4-binding protein, positively regulated HBV antigen and RNA expression; however, CNBP did not enhance CP/EN promoter activity, indicating a regulatory mechanism independent of CP/EN activation. This study reveals that two G4 structures within the HBV CP/EN regulatory region function as structural platforms for host factor recruitment and play distinct roles in regulating viral gene expression. In particular, the 1732 G4 facilitates HNF4A-dependent activation of CP/EN activity, thereby supporting efficient viral protein production, whereas CNBP promotes HBV expression through a CP/EN-independent mechanism.

Five-Year Follow-Up of an Eight-Year-Old Boy With a Scleral-Fixated Carlevale Intraocular Lens After Ocular Trauma.

Drakou Zoi Z, Gotzaridis Stratos S, Kouri Agathi A, Maliagkani Eirini E

Management of pediatric aphakia without capsular support remains challenging, particularly following ocular trauma. Long-term outcomes of sutureless scleral fixation of the Carlevale intraocular lens (IOL) in children remain limited. We present the surgical management and five-year follow-up of a child with traumatic aphakia treated with a Carlevale IOL. An eight-year-old boy sustained a penetrating ocular injury caused by a knife, resulting in a full-thickness corneal laceration, traumatic cataract, and inadequate capsular support. Following primary corneal repair and lens removal elsewhere, the patient was referred to our clinic. A 25-gauge pars plana vitrectomy and sutureless scleral fixation of a Carlevale IOL were performed. At the five-year follow-up examination, the IOL remained well centered without tilt, haptic erosion, or significant inflammatory complications. Visual acuity improved progressively, reaching 0.0 LogMAR without refractive correction at the final examination. This case demonstrates a favorable anatomical and visual outcome at five years following sutureless scleral fixation of a Carlevale IOL in a child with traumatic aphakia and inadequate capsular support. The IOL remained stable at the five-year examination, with excellent uncorrected visual acuity and a favorable refractive outcome. This case suggests a potential role for the Carlevale IOL in the management of pediatric traumatic aphakia.

Approaching microaggressions toward ​a career in pathology: A potential path to a respectful culture.

Pleotis Howell Lydia L