Within host RNA virus persistence: mechanisms and consequences

Randall, Richard E.; Griffin, Diane E.

doi:10.1016/j.coviro.2017.03.001

Cited by 85 publications

(96 citation statements)

References 122 publications

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“…To the best of our knowledge, this is the first description of an experimentally proven persistent infection for astroviruses. RNA viruses make use of several mechanisms for persistence, including the innate immune system evasion, and most persistent infections are asymptomatic (51,52). Thereby, although continuous cell lines are not the best model to infer issues related to pathology occurring in vivo, it would be very interesting to further study if there is any role for persistent infection in astrovirus diseases, and if so, which are the determinants for the virus to switch from persistence to virulence.…”

Section: Discussionmentioning

confidence: 99%

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Bosch

Pintó

et al. 2019

J Virol

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MLB astroviruses were identified 10 years ago in feces from children with gastroenteritis of unknown etiology and have been unexpectedly detected in severe cases of meningitis/encephalitis, febrile illness of unknown etiology, and respiratory syndromes. The aim of this study was to establish a cell culture system supporting MLB astrovirus replication. We used two clinical strains to infect several cell lines, an MLB1 strain from a gastroenteritis case, and an MLB2 strain associated with a neurologic infection. Efforts to propagate the viruses in the Caco-2 cell line were unsuccessful. In contrast, we identified two human nonintestinal cell lines, Huh-7 and A549, permissive for both genotypes. After serial passages in the Huh-7.5 cell line, the adapted strains were able to establish persistent infections in the Huh-7.5, Huh-7AI, and A549 cell lines, with high viral loads (up to 10 log10 genome copies/ml) detected by quantitative reverse transcription-PCR (RT-qPCR) in the culture supernatant. Immunofluorescence assays demonstrated infection in about 10% of cells in persistently infected cultures. Electron microscopy revealed particles of 32 to 33 nm in diameter after negative staining of cell supernatants and capsid arrays in ultrathin sections with a particularly high production in Huh-7.5 cells. Interferon (IFN) expression by infected cells and effect of exogenous IFN varied depending on the type of infection and the cell line. The availability of a cell culture system to propagate MLB astroviruses represents a key step to better understand their replicative cycle, as well as a source of viruses to conduct a wide variety of basic virologic studies. IMPORTANCE MLB astroviruses are emerging viruses infecting humans. More studies are required to determine their exact epidemiology, but several reports have already identified them as the cause of unexpected clinical diseases, including severe neurologic diseases. Our study provides the first description of a cell culture system for the propagation of MLB astroviruses, enabling the study of their replicative cycle. Moreover, we demonstrated the unknown capacity of MLB astrovirus to establish persistent infections in cell culture. Whether these persistent infections are also established in vivo remains unknown, but the clinical consequences would be of high interest if persistence was confirmed in vivo. Finally, our analysis of IFN expression provides some trails to understand the mechanism by which MLB astroviruses can cause persistent infections in the assayed cultures.

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Section: Discussionmentioning

confidence: 99%

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Bosch

Pintó

et al. 2019

J Virol

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“…The exact mechanism(s) by which picornaviruses establish, maintain, and recrudesce from persistent infections is not completely understood. One of the requirements for establishment of persistent viral infections is the maintenance of the viral genome in persistently infected cells (37,38). To preserve genome stability during persistence, positive-stranded RNA viruses may maintain their genome as double-stranded RNA (dsRNA) in the absence of active replication (39) while other viruses establish persistence through continuous low-level replication in persistently infected cells (37,40).…”

Section: Discussionmentioning

confidence: 99%

Persistent Infection and Transmission of Senecavirus A from Carrier Sows to Contact Piglets

Maggioli

Fernandes

Joshi

et al. 2019

J Virol

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Senecavirus A (SVA) is a picornavirus that causes acute vesicular disease (VD), that is clinically indistinguishable from foot-and-mouth disease (FMD), in pigs. Notably, SVA RNA has been detected in lymphoid tissues of infected animals several weeks following resolution of the clinical disease, suggesting that the virus may persist in select host tissues. Here, we investigated the occurrence of persistent SVA infection and the contribution of stressors (transportation, immunosuppression, or parturition) to acute disease and recrudescence from persistent SVA infection. Our results show that transportation stress leads to a slight increase in disease severity following infection. During persistence, transportation, immunosuppression, and parturition stressors did not lead to overt/recrudescent clinical disease, but intermittent viremia and virus shedding were detected up to day 60 postinfection (p.i.) in all treatment groups following stress stimulation. Notably, real-time PCR and in situ hybridization (ISH) assays confirmed that the tonsil harbors SVA RNA during the persistent phase of infection. Immunofluorescence assays (IFA) specific for double-stranded RNA (dsRNA) demonstrated the presence of double-stranded viral RNA in tonsillar cells. Most importantly, infectious SVA was isolated from the tonsil of two animals on day 60 p.i., confirming the occurrence of carrier animals following SVA infection. These findings were supported by the fact that contact piglets (11/44) born to persistently infected sows were infected by SVA, demonstrating successful transmission of the virus from carrier sows to contact piglets. Results here confirm the establishment of persistent infection by SVA and demonstrate successful transmission of the virus from persistently infected animals. IMPORTANCE Persistent viral infections have significant implications for disease control strategies. Previous studies demonstrated the persistence of SVA RNA in the tonsil of experimentally or naturally infected animals long after resolution of the clinical disease. Here, we showed that SVA establishes persistent infection in SVA-infected animals, with the tonsil serving as one of the sites of virus persistence. Importantly, persistently infected carrier animals shedding SVA in oral and nasal secretions or feces can serve as sources of infection to other susceptible animals, as evidenced by successful transmission of SVA from persistently infected sows to contact piglets. These findings unveil an important aspect of SVA infection biology, suggesting that persistently infected pigs may function as reservoirs for SVA.

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“…Viral exposures-and subsequent interactions with the host-are constant in the respiratory tract 42 . Furthermore, at least some viruses may persist 43 . Among these, prokaryotic viruses have been barely considered until now, despite their role in regulating bacterial abundance and promoting competition, stability and resilience 23,[44][45][46][47] within microbial ecosystems, which in turn may direct asthma development, activity and persistence 21,22,48,49 .…”

Section: Dysbiotic Structure Of the Asthmatic Viromementioning

confidence: 99%

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Megremis

Constantinides

Xepapadaki

et al. 2020

Preprint

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Asthma development and persistence is tightly linked to respiratory viruses. Viral presence is usually interrogated with targeted approaches during periods of disease activity and/or infections, thus neglecting viral occurrence during steady states. We investigate the virome in the upper respiratory system of healthy and asthmatic preschool children during asymptomatic/non-infection periods using metagenomics. Children with asthma have a characteristically dysbiotic virome that correlates to disease severity and control. The major component of dysbiosis is bacteriophage deficiency, while eukaryotic viral presence is increased. At the metacommunity level, differential virus species co-occurrence patterns suggest a decrease of the microbiota community resilience in asthma. Viral dysbiosis is therefore a key characteristic of asthma pathophysiology.

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Within host RNA virus persistence: mechanisms and consequences

Cited by 85 publications

References 122 publications

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Human Astrovirus MLB Replication In Vitro : Persistence in Extraintestinal Cell Lines

Persistent Infection and Transmission of Senecavirus A from Carrier Sows to Contact Piglets

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

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