Institute of Virology

Abstract

Thogotoviruses belong to the Orthomyxoviridae family in addition to the better known Influenza viruses that cause seasonal epidemics in humans.

In contrast to FLU-viruses, Thogotoviruses are arboviruses, meaning they rely on arthropod vectors for transmission between mammalian hosts. For most Thogotoviruses different ticks were identified as vector species.

Sporadic infections of humans and wild or domestic animals have been reported since the discovery of Thogotoviruses in the 1960’s in the Thogoto forest near Nairobi, Kenya. In recent years however, the zoonotic potential of these viruses has become more apparent after the previously unknown Bourbon virus was associated with the death of two patients in the US-Midwest.

With the increasing exposure of humans and domestic animals to ticks and the advance of invasive tick species due to habitat destruction and changing climate, zoonotic transmission events by Thogotoviruses might become more frequent in the future.

The aim of our project is to improve the understanding of the molecular biology and pathology of this unconventional class of orthomyxoviruses.

Like other Orthomyxoviruses, Thogotoviruses have a segmented genome of single stranded negative sense-RNA. Together, the six genome segments encode for 6-7 viral proteins:

The three largest segments contain the information for the subunits, PB1, PB2, and PA, that make up the viral RNA-dependent RNA polymerase (RdRP) responsible for replication of the viral genome and its transcription into positive-sense mRNA.

The fourth and fifth largest segments respectively encode a Glycoprotein (GP), the surface protein responsible for attachment and entry into the host cell, and the nucleoprotein (NP), which encapsidates and protects the viral RNA, forming the viral Ribonucleocapsid (vRNP). The smallest segment codes for the viral Matrix protein (M) responsible for packaging of the genome segments into newly forming viral particles. In some Thogotoviruses, this segment also contains the information for an accessory protein called Matrix long (ML) with immune-modulatory functions.

Our current research focuses on the intricate coding strategy of the smaller genome segments of Thogotoviruses as well as the interplay of Thogotoviruses with parts of the host innate immune system, such as the interferon-induced Mx-proteins.