Elsevier

Journal of Clinical Virology

Volume 64, March 2015, Pages 120-127
Journal of Clinical Virology

Research efforts to control highly pathogenic arenaviruses: A summary of the progress and gaps

https://doi.org/10.1016/j.jcv.2014.12.004Get rights and content

Highlights

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    This article reviews the progress made in research on Lassa virus and the South American arenaviruses in the past 10 years, and identifies gaps in our knowledge which need to addressed to better control the diseases.

Abstract

Significant progress has been made in the past 10 years in unraveling the molecular biology of highly pathogenic arenaviruses that are endemic in several West African countries (Lassa fever virus) and in some regions of South America (Argentine and Bolivian hemorrhagic fever viruses). While this has resulted in proof-of-concept studies of novel vaccine candidates in non-human primates and in the discovery of several novel antiviral small molecule drug candidates, none of them has been tested in the clinic to date. The recent Ebola outbreak in West Africa has demonstrated very clearly that there is an urgent need to develop the prophylactic and therapeutic armamentarium against viral hemorrhagic fever viruses as part of a global preparedness for future epidemics. As it pertains to this goal, the present article summarizes the current knowledge of highly pathogenic arenaviruses and identifies opportunities for translational research.

Section snippets

Lassa fever: advances in epidemiology, diagnosis, and therapy

Lassa fever (LF) is a rodent borne viral hemorrhagic disease that is endemic across many areas in western Africa and caused by the Lassa virus (LASV), which belongs to the old world serogroup of the genus arenaviruses. Infection occurs through exposure to excreta of infected rodents, or less often, person-to-person via body fluids. The case fatality rate of endemic Lassa fever is only around 1%, but the disease claims more lives than Ebola fever because its incidence is much higher. However, in

South American arenaviral hemorrhagic fevers: advances in epidemiology, diagnosis and therapy

South and North American arenaviruses belong to the New World serogroup of the genus arenaviruses. They generally infect rodents of the family Muridae, subfamily Sigmodontinae, which represent their reservoir hosts [34]. The viruses show circumscribed geographical distribution patterns related to the distribution of their hosts, and humans may occasionally be infected with aerosolized rodent excreta containing infectious virus that may enter the body through skin, respiratory tract, or

Progress in vaccine development against arenavirus infections

Currently there is no licensed vaccine against LASV available. In natural infection neutralizing antibodies appear late in the course of disease and their titers are usually too low to allow use of convalescent serum for passive immunotherapy. Recently, progress has been made in studying T-cell responses in Lassa fever infection. A direct role for T-cells in protection was demonstrated experimentally by showing that monkeys surviving LASV challenge have early and strong innate and adaptive

Progress in drug development against arenavirus infections

Arenavirus structure and a summary of the life cycle are shown in Fig. 1. Arenaviruses consist of two ribonucleoprotein particles (RNPs – viral proteins bound to the viral RNA genome) surrounded by a lipid envelope. The genome consists of two single-stranded RNA segments, called S (small) and L (large) with an ambisense coding strategy. The viral RNA per se is not infectious. The S RNA encodes the nucleocapsid protein (NP) and the glycoprotein precursor (GPC), which is posttranslationally

Conclusions

During the past years, an impressive progress has been made towards our understanding of the basic molecular and cellular biology of arenaviruses (Table 2). In particular, the development of a reverse genetics system for several arenaviruses represented an important breakthrough and provided a powerful tool to precisely address questions of fundamental biology and pathogenicity as well as novel vaccine candidates [79], [80], [81], [82], [83]. The studies on early molecular events of arenavirus

Funding

Stephan Günther, Romy Kerber and Sophia Reindl – DFG GU 883/4-1 “Pathophysiology, treatment, and epidemiology of Lassa fever in Nigeria” DFG GU 883/3-1. “Ecology of Lassa virus and related arenaviruses in the natural host M. natalensis”.

Jan ter Meulen – Not applicable.

Gomez RM – Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) PICT 2012-0434 (R.M.G.).

Víctor Romanowski – Universidad Nacional de La Plata (UNLP), Argentina) Agencia Nacional de Promoción Científica y Tecnológica

Competing interests

The authors declare no competing interests.

Ethical approval

No ethical approval is required for this review article.

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