<b>Short communication:</b> Lassa fever in Sierra Leone: UN peacekeepers are at risk

Meulen, Jan ter; Lenz, Oliver; Koivogui, Lamine; Magassouba, N’Faly; Kaushik, Sushil Kumar; Lewis, Rosamund; Aldis, William

doi:10.1046/j.1365-3156.2001.00676.x

Cited by 33 publications

(19 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to 20% of these patients develop hemorrhagic manifestations with a total mortality of 10 to 15% (28,29). In recent years this disease has been increasingly exported from regions where it is endemic to other parts of the world (36).…”

mentioning

confidence: 99%

Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles

Strecker

Eichler

Meulen

et al. 2003

J Virol

Self Cite

214

222

View full text Add to dashboard Cite

Lassa virus is an enveloped virus with glycoprotein spikes on its surface. It contains an RNA ambisense genome that encodes the glycoprotein precursor GP-C, the nucleoprotein NP, the polymerase L, and the Z protein. Here we demonstrate that the Lassa virus Z protein (i) is abundant in viral particles, (ii) is strongly membrane associated, (iii) is sufficient in the absence of all other viral proteins to release enveloped particles, and (iv) contains two late domains, PTAP and PPXY, necessary for the release of virus-like particles. Our data provide evidence that Z is the Lassa virus matrix protein that is the driving force for virus particle release.Lassa virus belongs to the large family of Arenaviridae, including the closely related Lymphocytic choriomeningitis virus (LCMV) and other important human pathogens like Guanarito virus, Junin virus, and Machupo virus. Lassa virus is the etiologic agent of a hemorrhagic fever endemic in West Africa, where annually up to 100,000 cases of clinically apparent Lassa fever occur. Up to 20% of these patients develop hemorrhagic manifestations with a total mortality of 10 to 15% (28,29). In recent years this disease has been increasingly exported from regions where it is endemic to other parts of the world (36).Lassa virus consists of a helical nucleocapsid containing a bisegmented RNA genome surrounded by a lipid bilayer with integrated glycoprotein spikes. Each single-stranded RNA encodes two viral genes in an ambisense coding strategy separated by an intergenic region. The small RNA encodes the nucleoprotein NP (60 kDa) and the immature glycoprotein precursor pre-GP-C (80 kDa), which is cotranslationally cleaved by signal peptidase into GP-C (75 kDa) and a stable signal peptide of 58 amino acids (aa) (10). GP-C is cleaved posttranslationally by subtilase SKI-1/S1P into the N-terminal subunit GP-1 (40 kDa) and the membrane-bound subunit GP-2 (35 kDa). Both subunits are incorporated in virus particles (24,25). The large RNA segment encodes the RNAdependent RNA polymerase L (ϳ200 kDa) and the Z protein with a length of 99 amino acids and a molecular mass of approximately 11 kDa (33,35).During the last few years, the role of the arenavirus Z protein has been elucidated in respect to virus replication. The Z protein of Lassa virus and LCMV contains a RING motif and was shown to have zinc-binding activity (34). Most of the information so far indicates a regulatory role of Z, as the LCMV Z protein was shown to bind to the promyelotic leukemia protein and to relocate nuclear structures formed by the promyelotic leukemia protein (2, 4). The LCMV Z protein has also been reported to interact with the nuclear fraction of the ribosomal protein P0 and with the eukaryotic translation initiation factor eIF4E (3, 7). Furthermore, the Z protein of Tacaribe virus is implicated in RNA synthesis and genome replication in the early stage of infection (13). In contrast, the Z protein of LCMV was not required for RNA replication and transcription in a LCMV minigenome system. Moreover, the Z pro...

show abstract

mentioning

confidence: 99%

Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles

Strecker

Eichler

Meulen

et al. 2003

J Virol

Self Cite

214

222

View full text Add to dashboard Cite

show abstract

“…The civil instability in the region has resulted in large-scale human displacement and the creation of large populations of refugees, many of them in camps in southeastern Guinea. Consequently, Lassa fever may pose a threat to refugees, aid workers, and United Nations peacekeepers exposed in the area, in addition to the indigenous populations (Allan et al 1998, ter Meulen et al 2001. Mastomys are ubiquitous in the region, but there is considerable heterogeneity in geographic distribution of LASV-infected rodents .…”

Section: Introductionmentioning

confidence: 99%

Lassa Virus-Infected Rodents in Refugee Camps in Guinea: A Looming Threat to Public Health in a Politically Unstable Region

Fair

Jentes

Inapogui³

et al. 2007

Vector-Borne and Zoonotic Diseases

View full text Add to dashboard Cite

Rodent-borne and other communicable diseases are of particular concern to vulnerable populations in complex humanitarian emergencies. We assessed the risk of Lassa fever to refugees and humanitarian aid workers in the Forest Region of Guinea by trapping rodents and testing them for the presence of Lassa virus infection. Our study provides a point prevalence of Lassa virus-infected rodents in various refugee camps in Guinea, suggesting that the risk of disease may be highest in camps further south toward the border with Liberia. The methodology used represents a potential model for rapid public health assessments in the setting of complex humanitarian emergencies.

show abstract

“…Lassa virus causes annually up to 100,000 cases of clinically apparent Lassa fever in West Africa, with 10% to 20% of the patients developing hemorrhagic manifestations and a total mortality of around 15% (1,2). The disease is also increasingly exported from endemic regions to other parts of the world (3).…”

mentioning

confidence: 99%

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P

Lenz

Meulen

Klenk

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

331

349

View full text Add to dashboard Cite

The surface glycoprotein of the Lassa virus, a member of the arenaviridae family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and a C-terminal membrane-anchored 36-kDa subunit. Cleavage occurs at the C-terminal end of the unusual recognition motif R-R-L-L. We show here that GP-C is cleaved in the endoplasmic reticulum by the cellular subtilase SKI-1͞S1P, an enzyme that has so far been observed to be involved in cholesterol metabolism. Furthermore, we present evidence that only cleaved glycoprotein is incorporated into virions and that this is necessary for the formation of infectious virus. To our knowledge, there have been no previous reports of this type of viral glycoprotein processing, one that may be an interesting target for antiviral therapy.

show abstract

Short communication: Lassa fever in Sierra Leone: UN peacekeepers are at risk

Cited by 33 publications

References 3 publications

Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles

Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like Particles

Lassa Virus-Infected Rodents in Refugee Camps in Guinea: A Looming Threat to Public Health in a Politically Unstable Region

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P

Contact Info

Product

Resources

About