Roles and mechanisms of exosomal microRNAs in viral infections.

Exosomes are small extracellular vesicles with a diameter of 30-150 nm that originate from endosomes and fuse with the plasma membrane. They are secreted by almost all kinds of cells and can stably transfer different kinds of cargo from donor to recipient cells, thereby altering cellular functions for assisting cell-to-cell communication. Exosomes derived from virus-infected cells during viral infections are likely to contain different microRNAs (miRNAs) that can be transferred to recipient cells. Exosomes can either promote or suppress viral infections and therefore play a dual role in viral infection. In this review, we summarize the current knowledge about the role of exosomal miRNAs during infection by six important viruses (hepatitis C virus, enterovirus A71, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, and Zika virus), each of which causes a significant global public health problem. We describe how these exosomal miRNAs, including both donor-cell-derived and virus-encoded miRNAs, modulate the functions of the recipient cell. Lastly, we briefly discuss their potential value for the diagnosis and treatment of viral infections.

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

[Reactivation of Epstein-Barr virus (Herpesviridae: Lymphocryptovirus, HHV-4) infection during COVID-19: epidemiological features].

INTRODUCTION: Immunodeficiency underlying the development of severe forms of new coronavirus infection may be the result of mixed infection with SARS-CoV-2 and other pathogens, including Epstein-Barr virus (EBV).The aim is to study the prevalence and epidemiological features of co-infection with SARS-CoV-2 and EBV. MATERIAL AND METHODS: A cross-sectional randomized study was conducted in Moscow region from March to May 2020. Two groups were examined for EBV-markers: hospital patients (n = 95) treated for SARS-CoV-2 infection and blood donors (n = 92). RESULTS: With equal EBV prevalence the detection of active infection markers in donors (10.9%) was noticeably lower than in SARS-CoV-2 patients (80%). Significant differences in this indicator were also found when patients from subgroups with interstitial pneumonia with the presence (96.6%) and absence (97.2%) of SARS-CoV-2 in the nasopharyngeal smear were compared with the subgroup of patients with mild COVID-19 (43.3%). The average IgG VCA and IgG EBNA positivity coefficients in donor group were higher than in patient group (p < 0.05). Patients with active EBV infection markers were significantly more likely to have pneumonia, exceeding the reference values of ALT and the relative number of monocytes (odds ratio - 23.6; 3.5; 9.7, respectively). DISCUSSION: The present study examined the incidence and analyzed epidemiological features of active EBV infection in patients with COVID-19. CONCLUSION: A significantly higher rate of detection of active EBV infection markers in hospital patients indicates a combined participation SARS-CoV-2 and EBV in the development of interstitial pneumonia. Low levels of specific IgG EBV serve as predictors of EBV reactivation. Exceeding the reference values of ALT and the relative number of monocytes in patients should serve as a reason for examination for active EBV infection markers.

Magnesium in Infectious Diseases in Older People.

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.