Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus

The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (

Section: Discussioncontrasting

confidence: 48%

“…Therefore, this strain is very close to the LV currently circulating in zones of endemicity, and it has been subjected to a limited number of passages since its isolation from the patient's serum (34). In addition, both strains are considered highly pathogenic LV strains (4).…”

Section: Methodsmentioning

confidence: 99%

Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus

Pannetier¹,

Reynard²,

Russier³

et al. 2011

“…It has been shown that the lymphocytic choriomeningitis virus, an Old World Arenavirus, harboring a D382 substitution in NP (equivalent to 389 in LASV NP) grows to a slightly decreased level in IFN-deficient cells and is dramatically attenuated in IFN-competent cells (4). Moreover, IFN-␣ has been shown to regulate LASV replication (33). Together, these data suggest that the exonuclease activity upstream to the anti-IFN function of LASV NP is required for replication in APC, but we believe that it is mostly due to an indirect effect including a strong type I IFN response.…”

Section: Discussionmentioning

confidence: 99%

The Exonuclease Domain of Lassa Virus Nucleoprotein Is Involved in Antigen-Presenting-Cell-Mediated NK Cell Responses

Russier

Reynard

Carnec

et al. 2014

“…Isolation of viral RNA from the cell culture supernatant was performed as described previously (1). The isolated RNA from the supernatant was detected by real-time reverse transcription-PCR (RT-PCR) using the Brilliant single-step quantitative RT-PCR kit (Stratagene).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Filovirus Replication by the Zinc Finger Antiviral Protein

Müller

Möller

Bick

et al. 2007

Self Cite

181

170

The zinc finger antiviral protein (ZAP) was recently shown to inhibit Moloney murine leukemia virus and Sindbis virus replication. We tested whether ZAP also acts against Ebola virus (EBOV) and Marburg virus (MARV). Antiviral effects were observed after infection of cells expressing the N-terminal part of ZAP fused to the product of the zeocin resistance gene (NZAP-Zeo) as well as after infection of cells inducibly expressing full-length ZAP. EBOV was inhibited by up to 4 log units, whereas MARV was inhibited between 1 to 2 log units. The activity of ZAP was dependent on the integrity of the second and fourth zinc finger motif, as tested with cell lines expressing NZAP-Zeo mutants. Heterologous expression of EBOV-and MARV-specific sequences fused to a reporter gene suggest that ZAP specifically targets L gene sequences. The activity of NZAP-Zeo in this assay was also dependent on the integrity of the second and fourth zinc finger motif. Time-course experiments with infectious EBOV showed that ZAP reduces the level of L mRNA before the level of genomic or antigenomic RNA is affected. Transient expression of ZAP decreased the activity of an EBOV replicon system by up to 95%. This inhibitory effect could be partially compensated for by overexpression of L protein.In conclusion, the data demonstrate that ZAP exhibits antiviral activity against filoviruses, presumably by decreasing the level of viral mRNA. Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae.Their genome consists of a singlestranded RNA genome of negative polarity with a length of about 19 kb. The filovirus genome is transcribed in monocistronic mRNA species, which encode seven structural proteins: a single surface protein (GP), a matrix protein (virus protein 40 [VP40]), a second minor matrix protein (VP24), and four nucleocapsid proteins (nucleoprotein [NP], L protein, VP35, and VP30) (7,15,16,18,25). Both EBOV and MARV cause severe hemorrhagic fever in humans and nonhuman primates (4,19). Infections with filoviruses are characterized by high fever, hemorrhages, and shock (19,22). For Zaire-EBOV and MARV, mortality rates up to 90% have been described; the mortality rates for Sudan-EBOV are about 60% (from the Centers for Disease Control and Prevention website [http: //www.cdc.gov/]). To date, neither a vaccine nor a therapy for treating infected patients is available.In contrast to many other viruses, no host cell proteins with antiviral activity have been identified so far for filoviruses. However, it is known that filoviruses antagonize the interferon (IFN) response (17), suggesting that the IFN pathway plays a role in the host cell response against filoviruses. Both VP35 and VP24 of EBOV have been found to be involved in the IFN antagonism (6,12,23).In an attempt to search for host cell antiviral proteins active against filoviruses, we analyzed the effect of the CCCH-type zinc finger antiviral protein (ZAP) (8) on EBOV and MARV replication. ZAP was discovered via its ability to inhibit Moloney murine leukemia virus (MMLV)...