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[PMID]: | 28794024 |
[Au] Autor: | Huang C; Kolokoltsova OA; Mateer EJ; Koma T; Paessler S |
[Ad] Endereço: | Department of Pathology and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA chhuang@utmb.edu slpaessl@utmb.edu. |
[Ti] Título: | Highly Pathogenic New World Arenavirus Infection Activates the Pattern Recognition Receptor Protein Kinase R without Attenuating Virus Replication in Human Cells. |
[So] Source: | J Virol;91(20), 2017 Oct 15. | [Is] ISSN: | 1098-5514 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | The arenavirus family consists of several highly pathogenic viruses, including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junin virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. JUNV and MACV infections readily induce an interferon (IFN) response in human cells, while LASV infection usually triggers an undetectable or weak IFN response. JUNV induces an IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs (vRNAs) during infection and activates IFN response. Double-stranded-RNA (dsRNA)-activated protein kinase R (PKR) is another host non-self RNA sensor classically known for its vRNA recognition activity. Here we report that infection with NW arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor α subunit of eukaryotic initiation factor 2 (eIF2α). Host protein synthesis was substantially suppressed in MACV- and JUNV-infected cells but was only marginally reduced in LASV-infected cells. Despite the antiviral activity known for PKR against many other viruses, the replication of JUNV and MACV was not impaired but was slightly augmented in wild-type (wt) cells compared to that in PKR-deficient cells, suggesting that PKR or PKR activation did not negatively affect JUNV and MACV infection. Additionally, we found an enhanced IFN response in JUNV- or MACV-infected PKR-deficient cells, which was inversely correlated with virus replication. The detection of viral RNA by host non-self RNA sensors, including RIG-I and MDA5, is critical to the initiation of the innate immune response to RNA virus infection. Among pathogenic arenaviruses, the OW LASV usually does not elicit an interferon response. However, the NW arenaviruses JUNV and MACV readily trigger an IFN response in a RIG-I-dependent manner. Here, we demonstrate for the first time that pathogenic NW arenaviruses JUNV and MACV, but not the OW arenavirus LASV, activated the dsRNA-dependent PKR, another host non-self RNA sensor, during infection. Interestingly, the replication of JUNV and MACV was not restricted but was rather slightly augmented in the presence of PKR. Our data provide new evidence for a distinct interplay between host non-self RNA sensors and pathogenic arenaviruses, which also provides insights into the pathogenesis of arenaviruses and may facilitate the design of vaccines and treatments against arenavirus-caused diseases. |
[Mh] Termos MeSH primário: |
Arenavirus do Novo Mundo/patogenicidade Arenavirus do Velho Mundo/patogenicidade Imunidade Inata Vírus Junin/patogenicidade Receptores de Reconhecimento de Padrão/metabolismo Replicação Viral eIF-2 Quinase/metabolismo
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[Mh] Termos MeSH secundário: |
Células A549 Arenavirus do Novo Mundo/fisiologia Arenavirus do Velho Mundo/fisiologia Interações Hospedeiro-Patógeno Seres Humanos Interferons/biossíntese Interferons/imunologia Vírus Junin/fisiologia Fosforilação Receptores de Reconhecimento de Padrão/genética Fatores de Transcrição/metabolismo eIF-2 Quinase/genética
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Receptors, Pattern Recognition); 0 (Transcription Factors); 181233-60-3 (ELF2 protein, human); 9008-11-1 (Interferons); EC 2.7.11.1 (EIF2AK2 protein, human); EC 2.7.11.1 (eIF-2 Kinase) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171024 |
[Lr] Data última revisão:
| 171024 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170811 |
[St] Status: | MEDLINE |
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