Nipah virus persists in the brains of nonhuman primate survivors

Li, Jun; Coffin, Kayla M.; Johnston, Sara C.; Babka, April M.; Bell, Todd M.; Long, Simon Y.; Honko, Anna N.; Kuhn, Jens H.; Zeng, Xiankun

doi:10.1172/jci.insight.129629

Cited by 30 publications

(30 citation statements)

References 31 publications

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“…We have previously reported the development of RNAscope ISH assays to detect various high-consequence viruses including Ebola virus (EBOV; Filoviridae : Ebolavirus ), Marburg virus (MARV; Filoviridae : Marburgvirus ), Lassa virus (LASV; Arenaviridae : Mammarenavirus ), and Nipah virus (NiV; Paramyxoviridae : Henipavirus ) in FFPE animal tissues (26-29). Here we report the successful use of the RNAscope ISH assay to detect SARS-CoV-2 RNA in FFPE cell pellets using three probes: two probes binding the SARS-CoV-2 positive-sense (genomic) RNA and one probe binding the negative-sense (replicative intermediate) RNA (Figure 2A–F, Supplemental Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Single-stranded RNA viruses, such as SARS-CoV-2, have to generate a replicative intermediate RNA as a template to synthesize progeny genomic RNAs. We have previously reported the use of mFISH to detect EBOV, MARV, and NiV replication in FFPE tissues (26, 28, 29). Here, we tested mFISH to detect SARS-CoV-2 replication in FFPE specimens using positive-sense RNA probe 2 and negative-sense RNA probe 2 (Supplemental Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Single-stranded RNA viruses have to produce a replicative intermediate, antigenomic RNA, as a template to synthesize new genomic RNAs. Presence of such replicative intermediate RNA in tissues indicates ongoing viral replication (26, 28, 29). The commercially available RNAscope ISH assays, including chromogenic and fluorescent assays, we characterized here, can be applied to detect viral RNA in both human and animal tissue samples.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

Liu

Babka

Kearney

et al. 2020

Preprint

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AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019. The virus rapidly spread globally, resulting in a public-health crisis including more than one million cases and tens of thousands of deaths. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected formalin fixed paraffin embedded (FFPE) cell pellets. We identified a suitable rabbit polyclonal anti-SARS-CoV spike protein antibody and a mouse monoclonal anti-SARS-CoV nucleocapsid protein (NP) antibody for cross detection of the respective SARS-CoV-2 proteins by immunohistochemistry (IHC) and immunofluorescence assay (IFA). Next, we established RNAscope in situ hybridization (ISH) to detect SARS-CoV-2 RNA. Furthermore, we established a multiplex fluorescence ISH (mFISH) to detect positive-sense SARS-CoV-2 RNA and negative-sense SARS-CoV-2 RNA (a replicative intermediate indicating viral replication). Finally, we developed a dual staining assay using IHC and ISH to detect SARS-CoV-2 antigen and RNA in the same FFPE section. These reagents and assays will accelerate COVID-19 pathogenesis studies in humans and in COVID-19 animal models.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

Liu

Babka

Kearney

et al. 2020

Preprint

Self Cite

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“…Even neuropsychiatric sequelae have been reported but it remains unclear whether a post-infectious encephalo-myelitis occurs following infection [141][142][143]. The use of animal models showed that the main route of entry into the CNS is the olfactory nerve [144] and that the Nipah virus may persist in different regions of the brain of grivets/green monkeys [145], reminiscent of relapsing and late-onset encephalitis observed in humans [146].…”

Section: Respiratory Viruses With Neuroinvasive and Neurotropic Propementioning

confidence: 99%

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Desforges

Coupanec

Dubeau

et al. 2019

Viruses

940

997

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Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

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“…Survivors of acute NiV infection may suffer a lethal relapse-encephalitis 8 -13 months after initial disease resolution (Fig. 3B) (53)(54)(55).…”

Section: Niv Binds Ephrin-b2 or Ephrin-b3 And Can Cause Lethal Systemmentioning

confidence: 99%

Receptor-mediated cell entry of paramyxoviruses: Mechanisms, and consequences for tropism and pathogenesis

Navaratnarajah

Generous

Yousaf

et al. 2020

Journal of Biological Chemistry

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Research in the last decade has uncovered many new paramyxoviruses, airborne agents that cause epidemic diseases in animals including humans. Most paramyxoviruses enter epithelial cells of the airway using sialic acid as a receptor and cause only mild disease. However, others cross the epithelial barrier and cause more severe disease. For some of these viruses, the host receptors have been identified, and the mechanisms of cell entry have been elucidated. The tetrameric attachment proteins of paramyxoviruses have vastly different binding affinities for their cognate receptors, which they contact through different binding surfaces. Nevertheless, all input signals are converted to the same output: conformational changes that trigger refolding of trimeric fusion proteins and membrane fusion. Experiments with selectively receptor-blinded viruses inoculated into their natural hosts have provided insights into tropism, identifying the cells and tissues that support growth and revealing the mechanisms of pathogenesis. These analyses also shed light on diabolically elegant mechanisms used by morbilliviruses, including the measles virus, to promote massive amplification within the host, followed by efficient aerosolization and rapid spread through host populations. In another paradigm of receptor-facilitated severe disease, henipaviruses, including Nipah and Hendra viruses, use different members of one protein family to cause zoonoses. Specific properties of different paramyxoviruses, like neurotoxicity and immunosuppression, are now understood in the light of receptor specificity. We propose that research on the specific receptors for several newly identified members of the Paramyxoviridae family that may not bind sialic acid is needed to anticipate their zoonotic potential and to generate effective vaccines and antiviral compounds.

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Nipah virus persists in the brains of nonhuman primate survivors

Cited by 30 publications

References 31 publications

Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Receptor-mediated cell entry of paramyxoviruses: Mechanisms, and consequences for tropism and pathogenesis

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