Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

The apparent lack of antigenic evolution by the Delta variant (B.1.617.2) of SARS-CoV-2 during the COVID-19 pandemic is puzzling. The combination of increasing immune pressure due to the rollout of vaccines and a relatively high number of infections following the relaxation of non-pharmaceutical interventions should have created perfect conditions for immune escape variants to evolve from the Delta lineage. Instead, the Omicron variant (B.1.1.529), which is hypothesised to have evolved in an immunocompromised individual, is the first major variant to exhibit significant immune escape following vaccination programmes and is set to become globally dominant in 2022. Here, we use a simple mathematical model to explore possible reasons why the Delta lineage did not exhibit antigenic evolution and to understand how and when immunocompromised individuals affect the emergence of immune escape variants. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur, immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level, then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.

The combined impact of persistent infections and human genetic variation on C-reactive protein levels

Multiple human pathogens establish chronic, sometimes life-long infections. Even if they are often latent, these infections can trigger some degree of local or systemic immune response, resulting in chronic low-grade inflammation. There remains an incomplete understanding of the potential contribution of both persistent infections and human genetic variation on chronic low-grade inflammation. We searched for potential associations between seropositivity for 13 persistent pathogens and the plasma levels of the inflammatory biomarker C-reactive protein (CRP), using data collected in the context of the UK Biobank and the CoLaus|PsyCoLaus Study, two large population-based cohorts. We performed backward stepwise regression starting with the following potential predictors: serostatus for each pathogen, polygenic risk score for CRP, as well as demographic and clinical factors known to be associated with CRP. We found evidence for an association between Chlamydia trachomatis (P-value = 5.04e-3) and Helicobacter pylori (P-value = 8.63e-4) seropositivity and higher plasma levels of CRP. We also found an association between pathogen burden and CRP levels (P-value = 4.12e-4). These results improve our understanding of the relationship between persistent infections and chronic inflammation, an important determinant of long-term morbidity in humans.

Torque Teno Virus in Nasopharyngeal Aspirate of Children With Respiratory Infections

Torque teno virus (TTV) is responsible for persistent infections and is considered a marker of immune function. The role of TTV as a facilitator of respiratory infections(RIs) is unknown. We aimed to estimate the prevalence of TTV in the nasopharyngeal aspirate (NPA) of hospitalized children with RIs and correlate them with outcomes and immune response. NPA was taken for testing 16 respiratory viruses by RT-polymerase chain reaction (PCR), TTV PCR, and immunological study.Sixty hospitalized children with an RI and 3 healthy control infants were included. A total of 51/60 patients had a positive common respiratory viral (CRV) identification. A total of 24/63 (38.1%) children were TTV+ and had other CRVs in 95.8% of cases vs 74.4% in TTV- (p=0.029). TTV+ patients tended to be older, have fever, and need PICU admission more often than TTV- patients. Abnormal chest X-ray was more frequent in the TTV+ patients, OR 2.6(95% CI:1.3-5.2).The genetic expression of filaggrin (involved in epithelial barrier integrity) was lower in TTV+ patients; however, levels of filaggrin in the NPA were increased.In summary, TTV infection is common in children with RI and could be associated with pneumonia, greater severity, and alteration in filaggrin gene expression and protein release.

Shrimp draft genome contains independent clusters of ancient and current endogenous viral elements (EVE) of the parvovirus IHHNV

Shrimp have the ability to accommodate viruses in long term, persistent infections without signs of disease. Endogenous viral elements (EVE) play a role in this process probably via production of negative-sense Piwi-interacting RNA (piRNA)-like fragments. These bind with Piwi proteins to dampen viral replication via the RNA interference (RNAi) pathway. We searched a draft genome of the giant tiger shrimp (Penaeus monodon)(GenBank record JABERT000000000) for the presence of EVE related to a shrimp parvovirus originally named infectious hypodermal and hematopoietic necrosis virus (IHHNV). The shrimp draft genome contained 3 piRNA-like gene clusters containing scrambled IHHNV EVE. Two clusters were located distant from one another in linkage group 35 (LG35). Both LG35 clusters contained multiple DNA fragments with high homology (99%) to GenBank records DQ228358 and EU675312 that were both called non-infectious IHHNV Type A (IHHNV-A) when originally discovered. However, our results and those from a recent Australian P. monodon genome assembly indicate that the relevant GenBank records for IHHNV-A are sequence-assembly artifacts derived from scrambled and fragmental IHHNV-EVE. Although the EVE in the two LG35 clusters showed high homology only to IHHNV-A, the clusters were separate and distinct with respect to the arrangement (i.e., order and reading direction) and proportional content of the IHHNV-A GenBank records. We conjecture that these 2 clusters may constitute independent allele-like clusters on a pair of homologous chromosomes. The third EVE cluster was found in linkage group 7 (LG7). It contained EVE with high homology (99%) only to GenBank record AF218266 with the potential to protect shrimp against infectious IHHNV. Our results suggested the possibility of viral-type specificity in EVE clusters. Specificity is important whole EVE clusters for one viral type would be transmitted to offspring as collective hereditary units. This would be advantageous if one or more of the EVE within the cluster were protective against disease caused by the cognate virus. It would also facilitate gene editing for removal of non-protective EVE clusters or for transfer of protective EVE clusters to genetically improve existing shrimp breeding stocks that might lack them.

Involvement of Small Colony Variant-Related Heme Biosynthesis Genes in Staphylococcus aureus Persister Formation in vitro

Background: Persisters are important reasons for persistent infections, and they can lead to antibiotic treatment failure in patients and consequently chronic infection. Staphylococcus aureus small colony variants (SCVs) have been shown to be related to persistent infection. Mutations in the genes of the heme biosynthesis pathway lead to the formation of SCVs. However, the relationship between heme production genes and persister has not been tested.Methods:HemA and hemB were knocked out by allelic replacement from S. aureus strain USA500 separately, and then, the heme deficiency was complemented by overexpression of related genes and the addition of hemin. The stress-related persister assay was conducted. RNA-sequencing was performed to find genes and pathways involved in heme-related persister formation, and relative genes and operons were further knocked out and overexpressed to confirm their role in each process.Results: We found that heme biosynthesis deficiency can lead to decreased persister. After complementing the corresponding genes or hemin, the persister levels could be restored. RNA-seq on knockout strains showed that various metabolic pathways were influenced, such as energy metabolism, amino acid metabolism, carbohydrate metabolism, and membrane transport. Overexpression of epiF and operon asp23 could restore USA500∆hemA persister formation under acid stress. Knocking out operon arc in USA500∆hemA could further reduce USA500∆hemA persister formation under acid and oxidative stress.Conclusion: Heme synthesis has a role in S. aureus persister formation.

Human Cytomegalovirus miR-UL70-3p Downregulates the H2O2-Induced Apoptosis by Targeting the Modulator of Apoptosis-1 (MOAP1)

Human Cytomegalovirus (HCMV) is a prototypic beta herpesvirus, causing persistent infections in humans. There are medications that are used to treat the symptoms; however, there is no cure yet. Thus, understanding the molecular mechanisms of HCMV replication and its persistence may reveal new prevention strategies. HCMV evasive strategies on the antiviral responses of the human host largely rely on its significant portion of genome. Numerous studies have highlighted the importance of miRNA-mediated regulation of apoptosis, which is an innate immune mechanism that eradicates virus-infected cells. In this study, we explore the antiapoptotic role of hcmv-miR-UL70-3p in HEK293T cells. We establish that hcmv-miR-UL70-3p targets the proapoptotic gene Modulator of Apoptosis-1 (MOAP1) through interaction with its 3’UTR region of mRNA. The ectopic expression of hcmv-miR-UL70-3p mimic significantly downregulates the H2O2-induced apoptosis through the translational repression of MOAP1. Silencing of MOAP1 through siRNA also inhibits the H2O2-induced apoptosis, which further supports the hcmv-miR-UL70-3p mediated antiapoptotic effect by regulating MOAP1 expression. These results uncover a role for hcmv-miR-UL70-3p and its target MOAP1 in regulating apoptosis.

RNA viral communities are structured by host plant phylogeny in oak and conifer leaves

Wild plants can suffer devastating diseases, experience asymptomatic, persistent infections, and serve as reservoirs for viruses of agricultural crops, yet we have a limited understanding of the natural plant virosphere. To access representatives of locally and globally distinct wild plants and investigate their viral diversity, we extracted and sequenced dsRNA from leaves from 16 healthy oak and conifer trees in the UC Davis Arboretum (Davis, California). From de novo assemblies, we recovered 389 RNA-dependent RNA polymerase (RdRp) gene sequences from 384 putative viral species, and a further 580 putative viral contigs were identified with virus prediction software followed by manual confirmation of virus annotation. Based on similarity to known viruses, most recovered viruses were predicted to infect plants or fungi, with the highest diversity and abundance observed in the Totiviridae and Mitoviridae families. Phyllosphere viral community composition differed significantly by host plant phylogeny, suggesting the potential for host-specific viromes. The phyllosphere viral community of one oak tree differed substantially from other oak viral communities and contained a greater proportion of putative mycoviral sequences, potentially due to the tree's more advanced senescence at the time of sampling. These results suggest that oaks and conifers harbor a vast diversity of viruses with as-yet unknown roles in plant health and phyllosphere microbial ecology.

REACTIVATION OF HEPATITIS B IN PATIENTS RECOVERING FROM COVID-19

Пандемия новой короновирусной инфекции, вызванной вирусом SARS-CoV-2, явилась вызовом системе здравоохранения во всем мире. На данный момент мы обладаем большей информацией об этом заболевании, проявляющемся в основном симптомами респираторной инфекции, от легких проявлении ОРВИ до тяжелого поражения легких. Также коронавирусная инфекция проявляется симптомами поражения ЖКТ чаще всего в виде рвоты, диареи и боли в животе. Кроме того, за год наблюдении, начиная с самого начала пандемии в Китае, описаны нарушения функции печени различного генеза у пациентов с коронавирусной инфекцией. Среди возможных причин называются прямое цитопатическое действие вируса, способного связываться с AПФ2β рецепторам гепато-билиарной системы, иммуноопосредованное повреждение гепатоцитов, в том числе при «цитокиновом шторме» и гепатотоксичности препаратов, применяемых при коронавирусной инфекции. Кроме этих механизмов повреждения печени есть еще реактивация хронических персистирующих инфекции. В частности, речь идет о реактивации хронического гепатита В. Статей, описывающих такие случаи, значительно меньше, чем тех, которые практически детально описывают различные изменения ферментов печени у пациентов, наблюдавшихся с коронавирусной инфекцией. Кроме бремени инфекции в манифестный период, есть не менее тяжелые последствия у реконвалесцентов или у тех, кто перенес заболевание в легкой форме, о чем мы и должны помнить, чтобы принимать необходимые меры в ближайшем и отдаленном периоде выздоровления после COVID-19. В данной статье мы приводим собственные наблюдения реактивации хронического гепатита В у 4 пациентов, перенесших COVID-19 в манифестной форме. The pandemic of the new coronavirus infection caused by the SARS-CoV-2 virus is a challenge to the health system around the world. At the moment, we have more information about this disease, which is manifested mainly by symptoms of a respiratory infection, from mild manifestations of ARVI to severe lung damage. Also, coronavirus infection often manifests itself as symptoms of a gastrointestinal disease, in the form of vomiting, diarrhea and abdominal pain. In addition, over a year of observation, starting from the very beginning of the pandemic in China, liver dysfunctions of various origins have been described in patients with coronavirus infection. Possible reasons include the direct cytopathic effect of the virus capable of binding to ACE2β receptors of the hepato-biliary system, immune-mediated damage to hepatocytes, including during a "cytokine storm" and hepatotoxicity of drugs used in coronavirus infection. In addition to these mechanisms of liver damage, there is also a reactivation of chronic persistent infections. In particular, we are talking about the reactivation of chronic hepatitis B. In addition to the burden of infection in the manifest period, there are no less severe consequences for convalescents or those who have suffered a mild illness, which we must remember in order to take the necessary measures in the near and distant period of recovery after COVID -19. In this article, we present our own observations of the reactivation of chronic hepatitis in 4 patients who underwent manifest COVID-19.

Antimicrobial and Anti-Biofilm Activity of Polymyxin E Alone and in Combination with Probiotic Strains of Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895 against Clinical Isolates of Selected Acinetobacter spp.: A Preliminary Study

Acinetobacter spp., the nosocomial pathogen, forms strong biofilms and is resistant to numerous antibiotics, causing persistent infections. This study investigates the antibacterial and anti-biofilm activity of polymyxin E alone and in combination with the cell-free supernatants (CFS) of the tested probiotic bacilli, Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895 against the selected Acinetobacter spp. starins. Three isolates of Acinetobacter spp., designated as Acinetobacter spp. isolate 1; Acinetobacter spp. isolate 2, and Acinetobacter spp. isolate 3, were collected from patients with burns, wounds, and blood infections, respectively. Bacterial identification and antibiotic susceptibility testing were conducted using the VITEK2 system. Auto-aggregation and coaggregation of the tested bacilli strains with the selected Acinetobacter spp. isolates were evaluated. A disk diffusion assay was used to identify the microorganism’s susceptibility to the selected antibiotics, alone and in combination with the CFS of the bacilli. The MIC and MBIC (minimum inhibitory and minimum biofilm inhibitory concentrations) of polymyxin E combined with bacilli CFS were determined. Acinetobacter spp. isolates were (i) sensitive to polymyxin E, (ii) able to form a strong biofilm, and (iii) resistant to the tested antibiotics and the CFS of tested bacilli. Significant inhibition of biofilm formation was noticed when CFS of the tested bacilli were combined with polymyxin E. The bacilli CFS showed synergy with polymyxin E against planktonic cells and biofilms of the isolated pathogens.