Viral and host heterogeneity and their effects on the viral life cycle

Jones, Jennifer E.; Sage, Valerie Le; Lakdawala, Seema S.

doi:10.1038/s41579-020-00449-9

Cited by 76 publications

(83 citation statements)

References 140 publications

(245 reference statements)

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“…Virus-host interactions trigger a set of mechanisms that eventually affect the expression of host genes involved in the regulation of the viral replicative cycle as well as the pathogenesis of the disease [Jones et al, 2020]. Whereas dysregulation of host protein-coding genes caused by KSHV infection is well explored, host ncRNAs and KSHV dependency remains poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

A non-coding RNA network involved in KSHV tumorigenesis

Naipauer

Solá

Salyakina

et al. 2021

Preprint

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Regulatory pathways involving non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNA) have gained great relevance due to their role in the control of gene expression modulation. Using RNA sequencing of KSHV Bac36 transfected mouse endothelial cells (mECK36) and tumors, we have analyzed the host and viral transcriptome to uncover the role lncRNA-miRNA-mRNA driven networks in KSHV tumorigenesis. The integration of the differentially expressed ncRNAs, with an exhaustive computational analysis of their experimentally supported targets, led us to dissect complex networks integrated by the cancer-related lncRNAs Malat, Neat1, H19, Meg3 and their associated miRNA-target pairs. These networks would modulate pathways related to KSHV pathogenesis, such as viral carcinogenesis, p53 signaling, RNA surveillance, and Cell cycle control. Finally, the ncRNA-mRNA analysis allowed us to develop signatures that can be used to an appropriate identification of druggable gene or networks defining relevant AIDS-KS therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

A non-coding RNA network involved in KSHV tumorigenesis

Naipauer

Solá

Salyakina

et al. 2021

Preprint

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“…There are numerable ways the microbiota could influence attachment and entry of IAV into host cells, IAV replication, maturation of viruses with host cells, egress and dissemination, and interaction between coinfecting viral and bacterial pathogens (Jones, Le Sage, & Lakdawala, 2020). It is already clear that changes in glycosylation of the host incurred during IAV infection influence subsequent Spn colonization, and similarly changes in glycosylation via Spn affect subsequent IAV infection (Ortigoza et al, 2018; Siegel et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus

et al. 2020

Preprint

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Secondary bacterial infection, especially with Streptococcus pneumoniae (Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection with Streptococcus pneumoniae reduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.

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“…The viral life cycle includes four steps: entry, replication, assembly, and egress [18][19][20][21] (Figure 1). At the entry step, an enveloped virus binds to a target receptor, the viral envelope fuses with the host cell membrane, and the viral nucleic acids are released into the cytoplasm.…”

Section: Some Interactions Of Enveloped Viruses With Host Cells Are Cmentioning

confidence: 99%

“…At the assembly step, viral proteins and nucleic acids are packed into a viral particle and the viral envelope is formed. At the egress step, mature viral particles leave the cell through the cellular membrane [18][19][20][21].…”

Section: Some Interactions Of Enveloped Viruses With Host Cells Are Cmentioning

confidence: 99%

“…The consequences of these changes can determine the clinical course and severity of the disease. The release of the gene material of many enveloped viruses into the cytoplasm of the cell occurs by fusion of the viral envelope with plasma membrane or with membranes of late endosomes (endolysosomes) formed during receptor-mediated endocytosis [18][19][20][21][64][65][66][67][68][69][70]. The inclusion of viral envelopes into the host cell membrane (either after direct fusion of after endosomal membrane recycling) should change both the lipid and protein composition of the cell membrane and cause rearrangements in the lipidic milieu and antigenic profile of the host cell membrane (Figure 1).…”

Section: Virus-induced Modulations Of the Lipid Composition Of Cell Mmentioning

confidence: 99%

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Cholesterol Recognition Motifs (CRAC) in the S Protein of Coronavirus: A Possible Target for Antiviral Therapy?

Dunina-Barkovskaya¹

2021

Management of Dyslipidemia

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Some interactions of enveloped viruses with the host cell membrane have a cholesterol-dependent component, which may account for clinical manifestations of the infectious disease and can be used for the development of antiviral drugs. These cholesterol-dependent interactions can be mediated by cholesterol-recognition amino-acid consensus (CRAC) motifs present in viral proteins. The S protein of the SARS-CoV and SARS-CoV2 coronaviruses contains CRAC motifs that can be involved in the process of virus entry into the cell. Besides, during viral envelope formation, CRAC motifs can be responsible for binding of cell membrane cholesterol, leading to depletion of cell membrane cholesterol and subsequent malfunctioning of cellular cholesterol-dependent proteins, destabilization and permeabilization of cell membranes and, ultimately, to the death of infected cells. Understanding the mechanisms of cholesterol-dependent virus–cell interactions and the role of CRAC-containing viral proteins in the pathogenesis of the disease can serve as the basis for the development of new drugs that prevent both coronavirus entry into the cell and the damage of the infected cell during the viral morphogenesis. The target for such drugs can be the S-protein/cholesterol interface. CRAC-containing peptides derived from viral proteins may be among these agents. These peptides can also be used as experimental tools to study cholesterol-dependent virus–cell interactions.

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Viral and host heterogeneity and their effects on the viral life cycle

Abstract: The strength or affinity of the interaction between a viral receptor-binding protein and its target ligand on a host cell.

Cited by 76 publications

References 140 publications

A non-coding RNA network involved in KSHV tumorigenesis

A non-coding RNA network involved in KSHV tumorigenesis

Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus

Cholesterol Recognition Motifs (CRAC) in the S Protein of Coronavirus: A Possible Target for Antiviral Therapy?

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