New World Arenavirus Biology

Abstract

Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions of years. Their emergence as infectious agents in humans coincided with changes in the environment and farming practices that caused explosions in their host rodent populations. Zoonosis into humans likely occurs because the pathogenic New World arenaviruses use human transferrin receptor 1 to enter cells. The mortality rate after infection with these viruses is high, but the mechanism by which disease is induced is still not clear. Possibilities include direct effects of cellular infection or the induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Here we provide a review of the ecology and molecular and cellular biology of New World arenaviruses, as well as a discussion of the current animal models of infection. The development of animal models, coupled with an improved understanding of the infection pathway and host response, should lead to the discovery of new drugs for treating infections.

Identification of a clinical compound losmapimod that blocks Lassa virus entry

“…Arenaviruses employ different cellular receptors for entry. The New World arenaviruses use human transferrin receptor (hTfR1) (Sarute and Ross, 2017), while Lujo virus, an Old World arenavirus, uses NRP2 and CD63 for entry (Raaben et al, 2017). Conversely, LCMV, which is a prototype arenavirus belonging to the Old World serotype, uses α-DG as the receptor for entry, the same as LASV (Cao et al, 1998).…”

“…LASV, along with the prototype arenavirus lymphocytic choriomeningitis virus (LCMV) and Lujo virus (LUJV), belong to the Old World mammarenaviruses (Radoshitzky et al, 2015). The New World complex also contains several viruses that cause viral hemorrhagic fever (VHF) in humans, including Machupo virus (MACV), Guanarito virus (GTOV), Junin virus (JUNV), Sabia virus (SABV), and Chapare virus (CHPV) (Sarute and Ross, 2017). LASV is phylogenetically closer to LCMV than the New World mammarenaviruses (Oldstone, 2002).…”

Coronavirus genomic RNA packaging

“…This process occurs with a high degree of efficiency, although noteworthy exceptions can be found. For example, retroviruses package abundant amounts of host 7SL RNA (Onafuwa-Nuga et al, 2006), and arenaviruses incorporate entire ribosomes (Sarute and Ross, 2017).…”

A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity

“…However, the use of these approaches with live LASV are complicated by the requirement of biosafety level 4 (BSL4) containment. The viral trans-acting factors (NP and L) and cis-acting regulatory sequences required for the formation of a functional virus ribonucleoprotein (vRNP) complex responsible for directing viral genome replication and gene transcription of the mammarenavirus genome have been defined (Emonet et al, 2011a;Sarute and Ross, 2017). We used this knowledge to engineer cell lines constitutively expressing synthetic functional vRNPs for LCMV (LCMV/vRNP) and LASV (LASV/vRNP) encoding reporter genes (LCMV/vRNP: Gaussia luciferase [Gluc] and green fluorescent protein [GFP]; LASV/vRNP: Gluc and ZsGreen [ZsG]) whose expression levels serve as an accurate surrogate of vRNP activity.…”