We have previously shown that the hepatitis C virus (HCV) E1E2 envelope glycoprotein can regulate HIV-1 long-terminal repeat (LTR) activity through disruption to NF-κB activation. This response is associated with upregulation of the endoplasmic reticulum (ER) stress response pathway. Here, we demonstrate that the SARS-CoV-2 S, M, and E but not the N structural protein can perform similar downmodulation of HIV-1 LTR activation, and in a dose-dependent manner, in both HEK293 and lung BEAS-2B cell lines. This effect is highest with the SARS-CoV-2 Wuhan S strain and decreases over time for the subsequent emerging variants of concern (VOC), with Omicron providing the weakest effect. We developed pseudo-typed viral particle (PVP) viral tools that allowed for the generation of cell lines constitutively expressing the four SARS-CoV-2 structural proteins and utilising the VSV-g envelope protein to deliver the integrated gene construct. Differential gene expression analysis (DGEA) was performed on cells expressing S, E, M, or N to determine cell activation status. Gene expression differences were found in a number of interferon-stimulated genes (ISGs), including IF16, IFIT1, IFIT2, and ISG15, as well as for a number of heat shock protein (HSP) genes, including HSPH1, HSPA6, and HSPBP1, with all four SARS-CoV-2 structural proteins. There were also differences observed in expression patterns of transcription factors, with both SP1 and MAVS upregulated in the presence of S, M, and E but not the N protein. Collectively, the results indicate that gene expression patterns associated with ER stress pathways can be activated by SARS-CoV-2 envelope glycoprotein expression. The results suggest the SARS-CoV-2 infection can modulate an array of cell pathways, resulting in disruption to NF-κB signalling, hence providing alterations to multiple physiological responses of SARS-CoV-2-infected cells.

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies.

Ebola virus disease (EVD) has traditionally been conceptualized as an acute, fulminant illness culminating in either death or apparent systemic viral clearance. However, clinical, virological, and genomic evidence gathered since the 2013–2016 West African epidemic demonstrates that Ebola virus (EBOV) can persist for months to years within immunologically privileged anatomical compartments, particularly the central nervous system, eye, and male reproductive tract, after blood viremia becomes undetectable. Importantly, the strength of evidence differs by endpoint: RT-PCR positivity demonstrates persistence of viral RNA, recovery in culture demonstrates replication-competent virus, and documented transmission requires epidemiological and, where available, genomic linkage. Persistent infection has been associated with clinically important outcomes, including relapsing meningoencephalitis, genomically supported sexual transmission long after recovery, and outbreak resurgence linked to persistent human viral lineages. Synthesizing evidence across human cohort studies, case reports, non-human primate models, and organoid systems, this review examines the anatomical, molecular, and immunological factors that may permit EBOV survival in privileged niches. Structural barriers and local immunoregulatory environments are established features of these compartments, whereas the contributions of defective viral genomes, cell-type-specific interferon responses, exosome- or cell-mediated spread, host immunogenetic variation, and acute-phase treatment to long-term reservoir establishment remain supported to differing degrees and, in several cases, are still mechanistic hypotheses. Although monoclonal antibodies and direct-acting antivirals have transformed acute-phase outcomes, their effects on established tissue reservoirs remain incompletely defined. key knowledge gaps establishing the relationship between viral RNA detection and true infectivity, defining correlates of protection against relapse, and determining how acute-phase therapeutic choice influences reservoir establishment remains essential for developing compartment-penetrant treatments, updating survivor care guidelines, and preventing future outbreak resurgences.