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Journal of Virology Sep 2022Reassortment, or genome segment exchange, increases diversity among viruses with segmented genomes. Previous studies on the limitations of reassortment have largely...
Reassortment, or genome segment exchange, increases diversity among viruses with segmented genomes. Previous studies on the limitations of reassortment have largely focused on parental incompatibilities that restrict generation of viable progeny. However, less is known about whether factors intrinsic to virus replication influence reassortment. Mammalian orthoreovirus (reovirus) encapsidates a segmented, double-stranded RNA (dsRNA) genome, replicates within cytoplasmic factories, and is susceptible to host antiviral responses. We sought to elucidate the influence of infection multiplicity, timing, and compartmentalized replication on reovirus reassortment in the absence of parental incompatibilities. We used an established post-PCR genotyping method to quantify reassortment frequency between wild-type and genetically barcoded type 3 reoviruses. Consistent with published findings, we found that reassortment increased with infection multiplicity until reaching a peak of efficient genome segment exchange during simultaneous coinfection. However, reassortment frequency exhibited a substantial decease with increasing time to superinfection, which strongly correlated with viral transcript abundance. We hypothesized that physical sequestration of viral transcripts within distinct virus factories or superinfection exclusion also could influence reassortment frequency during superinfection. Imaging revealed that transcripts from both wild-type and barcoded viruses frequently co-occupied factories, with superinfection time delays up to 16 h. Additionally, primary infection progressively dampened superinfecting virus transcript levels with greater time delay to superinfection. Thus, in the absence of parental incompatibilities and with short times to superinfection, reovirus reassortment proceeds efficiently and is largely unaffected by compartmentalization of replication and superinfection exclusion. However, reassortment may be limited by superinfection exclusion with greater time delays to superinfection. Reassortment, or genome segment exchange between viruses, can generate novel virus genotypes and pandemic virus strains. For viruses to reassort their genome segments, they must replicate within the same physical space by coinfecting the same host cell. Even after entry into the host cell, many viruses with segmented genomes synthesize new virus transcripts and assemble and package their genomes within cytoplasmic replication compartments. Additionally, some viruses can interfere with subsequent infection of the same host or cell. However, spatial and temporal influences on reassortment are only beginning to be explored. We found that infection multiplicity and transcript abundance are important drivers of reassortment during coinfection and superinfection, respectively, for reovirus, which has a segmented, double-stranded RNA genome. We also provide evidence that compartmentalization of transcription and packaging is unlikely to influence reassortment, but the length of time between primary and subsequent reovirus infection can alter reassortment frequency.
Topics: Animals; Coinfection; Genome, Viral; RNA, Double-Stranded; Reassortant Viruses; Reoviridae; Superinfection
PubMed: 36094315
DOI: 10.1128/jvi.00910-22 -
Infection and Immunity Oct 2015Seasonal influenza virus infection presents a major strain on the health care system. Influenza virus infection has pandemic potential, which was repeatedly observed... (Review)
Review
Seasonal influenza virus infection presents a major strain on the health care system. Influenza virus infection has pandemic potential, which was repeatedly observed during the last century. Severe disease may occur in the young, in the elderly, in those with preexisting lung disease, and in previously healthy individuals. A common cause of severe influenza pathogenesis is superinfection with bacterial pathogens, namely, Staphylococcus aureus and Streptococcus pneumoniae. A great deal of recent research has focused on the immune pathways involved in influenza-induced susceptibility to secondary bacterial pneumonia. Both innate and adaptive antibacterial host defenses are impaired in the context of preceding influenza virus infection. The goal of this minireview is to highlight these findings and synthesize these data into a shared central theme of pathogenesis.
Topics: Animals; Humans; Influenza A virus; Influenza, Human; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae; Superinfection
PubMed: 26216421
DOI: 10.1128/IAI.00298-15 -
Current Problems in Diagnostic Radiology 2022New challenges in imaging and management of COVID-19 pneumonia emerge as the pandemic continues across the globe. These arise not only due to the COVID-19 pneumonia but... (Review)
Review
New challenges in imaging and management of COVID-19 pneumonia emerge as the pandemic continues across the globe. These arise not only due to the COVID-19 pneumonia but also related to various superinfections and co-infections. Limited use of bronchoscopic and other aerosol generating procedures to obtain representative lower respiratory samples from these patient groups for accurate identification of organism, increases the responsibility of radiologists in suggesting the most likely cause of secondary infection. Imaging features of many of these infections overlap with features of COVID-19 pneumonia. In this review, we highlight imaging findings that can aid in the diagnosis of superinfections and co-infections in patients with COVID-19 pneumonia, and also help in predicting the likely causative organism.
Topics: COVID-19; Coinfection; Humans; Pandemics; SARS-CoV-2; Superinfection
PubMed: 34903396
DOI: 10.1067/j.cpradiol.2021.09.009 -
Gut Jun 2023Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy...
OBJECTIVE
Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo.
DESIGN
A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer.
RESULTS
The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection.
CONCLUSION
The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.
Topics: Humans; Mice; Animals; Rabbits; Hepatitis delta Antigens; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Superinfection; Hepatitis Delta Virus; Hepatitis B; Hepatitis B virus; Antibodies, Viral; Mice, Transgenic
PubMed: 35977815
DOI: 10.1136/gutjnl-2022-327216 -
PloS One 2021The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection.
PATIENTS AND METHODS
We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763.
RESULTS
Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively).
CONCLUSIONS
Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.
Topics: Bacterial Infections; COVID-19; Coinfection; Hospitalization; Humans; Mycoses; Prevalence; SARS-CoV-2; Superinfection; Treatment Outcome; Virus Diseases
PubMed: 33956882
DOI: 10.1371/journal.pone.0251170 -
Pneumonia (Nathan Qld.) Apr 2021It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a... (Review)
Review
BACKGROUND
It has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a worse outcome than either infection on its own. However, it is still unclear what exact roles co-infections and/or superinfections play in patients with COVID-19 infection.
MAIN BODY
This was an extensive review of the current literature regarding co-infections and superinfections in patients with SARS-CoV-2 infection. The definitions used were those of the Centers for Disease Control and Prevention (US), which defines coinfection as one occurring concurrently with the initial infection, while superinfections are those infections that follow on a previous infection, especially when caused by microorganisms that are resistant, or have become resistant, to the antibiotics used earlier. Some researchers have envisioned three potential scenarios of bacterial/SARS-CoV-2 co-infection; namely, secondary SARS-CoV-2 infection following bacterial infection or colonisation, combined viral/bacterial pneumonia, or secondary bacterial superinfection following SARS-CoV-2. There are a myriad of published articles ranging from letters to the editor to systematic reviews and meta-analyses describing varying ranges of co-infection and/or superinfection in patients with COVID-19. The concomitant infections described included other respiratory viruses, bacteria, including mycobacteria, fungi, as well as other, more unusual, pathogens. However, as will be seen in this review, there is often not a clear distinction made in the literature as to what the authors are referring to, whether true concomitant/co-infections or superinfections. In addition, possible mechanisms of the interactions between viral infections, including SARS-CoV-2, and other infections, particularly bacterial infections are discussed further. Lastly, the impact of these co-infections and superinfections in the severity of COVID-19 infections and their outcome is also described.
CONCLUSION
The current review describes varying rates of co-infections and/or superinfections in patients with COVID-19 infections, although often a clear distinction between the two is not clear in the literature. When they occur, these infections appear to be associated with both severity of COVID-19 as well as poorer outcomes.
PubMed: 33894790
DOI: 10.1186/s41479-021-00083-w -
Experimental and Therapeutic Medicine Jun 2023The future waves of COVID 19 infections will continue to raise serious problems in patients with severe forms of the disease. Bacterial infections associated with...
The future waves of COVID 19 infections will continue to raise serious problems in patients with severe forms of the disease. Bacterial infections associated with SARS-CoV-2 disease may complicate the progress of hospitalized patients with COVID-19. The present study aimed to evaluate the etiological spectrum of superinfection in adult patients with COVID-19 and to investigate the correlation between superinfection with multidrug-resistant (MDR) bacteria and serum procalcitonin (PCT). A total of 82 COVID-19 hospitalized patients with COVID-19 and bacterial superinfection were included. The superinfections were classified into early infections (3-7 days from admission) and late infections (>7 days from admission). Bacterial superinfection etiological spectrum, MDR bacteria profile and levels of serum PCT were studied. The most frequently isolated bacteria were , and MDR bacteria were involved in 73.17% of COVID-19 patients with bacterial superinfections. Most MDR bacteria superinfections (73.52%) occurred in the late infection period. , . and were the most common MDR bacteria identified in late infections after hospitalization in 20.43, 4.30 and 4.30% of all infections, respectively. Serum PCT values were significantly higher in patients with MDR bacteria superinfection compared with patients with sensitive bacteria superinfection (P=0.009). The principal findings of the present study were the high prevalence of superinfection with MDR bacteria among the COVID-19 patients with bacterial superinfections and the presence of a statistically significant association between serum PCT levels and the presence of superinfection with MDR bacteria. The most effective way to fight against microbial resistance to antibiotics, whether it occurs independently or overlaps with viral infections, is to pursue a national policy for the rational use of antibiotics.
PubMed: 37153889
DOI: 10.3892/etm.2023.11953 -
Journal of Virology Jan 2023Globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Cocirculation of several arboviruses in the same...
Globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Cocirculation of several arboviruses in the same geographic region provides an impetus to study the impacts of multiple concurrent infections within an individual vector mosquito. Here, we describe coinfection and superinfection with the Mayaro virus (Togaviridae, ) and Zika virus (Flaviviridae, ) in vertebrate and mosquito cells, as well as Aedes aegypti adult mosquitoes, to understand the interaction dynamics of these pathogens and effects on viral infection, dissemination, and transmission. Aedes aegypti mosquitoes were able to be infected with and transmit both pathogens simultaneously. However, whereas Mayaro virus was largely unaffected by coinfection, it had a negative impact on infection and dissemination rates for Zika virus compared to single infection scenarios. Superinfection of Mayaro virus atop a previous Zika virus infection resulted in increased Mayaro virus infection rates. At the cellular level, we found that mosquito and vertebrate cells were also capable of being simultaneously infected with both pathogens. Similar to our findings , Mayaro virus negatively affected Zika virus replication in vertebrate cells, displaying complete blocking under certain conditions. Viral interference did not occur in mosquito cells. Epidemiological and clinical studies indicate that multiple arboviruses are cocirculating in human populations, leading to some individuals carrying more than one arbovirus at the same time. In turn, mosquitoes can become infected with multiple pathogens simultaneously (coinfection) or sequentially (superinfection). Coinfection and superinfection can have synergistic, neutral, or antagonistic effects on viral infection dynamics and ultimately have impacts on human health. Here we investigate the interaction between Zika virus and Mayaro virus, two emerging mosquito-borne pathogens currently circulating together in Latin America and the Caribbean. We find a major mosquito vector of these viruses-Aedes aegypti-can carry and transmit both arboviruses at the same time. Our findings emphasize the importance of considering co- and superinfection dynamics during vector-pathogen interaction studies, surveillance programs, and risk assessment efforts in epidemic areas.
Topics: Animals; Humans; Aedes; Alphavirus; Alphavirus Infections; Coinfection; Mosquito Vectors; Superinfection; Vertebrates; Zika Virus; Zika Virus Infection
PubMed: 36598200
DOI: 10.1128/jvi.01778-22 -
MBio Feb 2024Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is necessary and sufficient for exclusion by the SieA system and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants that overcome the SieA block were isolated, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single-amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in phage target specificity. Our data strongly suggest a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.IMPORTANCEThe ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called "superinfection exclusion." A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.
Topics: Humans; Bacteriophage P22; Superinfection; Bacteriophages; Prophages; Membrane Proteins; DNA; Amino Acids
PubMed: 38236051
DOI: 10.1128/mbio.02169-23 -
Viruses Sep 2023The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear....
BACKGROUND
The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients.
METHODS
Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant was assessed.
RESULTS
The incidence of KPC-producing and/or carbapenem-resistant rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing and/or carbapenem-resistant occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24-1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18-12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43-9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40-0.72) were the features most strongly associated with in-hospital mortality.
CONCLUSIONS
Although KPC-producing and/or carbapenem-resistant rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.
Topics: Adult; Humans; Carbapenems; Anti-Bacterial Agents; Retrospective Studies; Prevalence; Superinfection; COVID-19; SARS-CoV-2; Klebsiella pneumoniae; Sepsis
PubMed: 37766340
DOI: 10.3390/v15091934