Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo

Wed, 08/05/2019

Publication

Publication by the International Center for Infectiology Research (CIRI) in Nature Communications on May 8, 2019.

Hepatitis D virus (HDV) was discovered 40 years ago in the liver of individuals chronically infected with hepatitis B virus (HBV), a liver-specific human pathogen that provides its surface GPs to induce envelopment and secretion of HDV RNPs as well as transmission to other cells via HBV cell entry factors. Although HDV worsens HBV pathogenicity, its origin is currently unknown. It is a satellite virus whose genome is unique among animal viruses but shares properties with plant viroids. As HDV efficiently replicates in different tissues and species, we raised the hypothesis that it may have arisen from and/or conceivably still infect hosts independently of HBV. Aiming to explore scenarios concerning the origin of HDV, we investigated the possibility that other, HBV-unrelated viruses could provide helper envelopment, budding, and entry functions.

Our results indicate that HDV RNPs may exploit assembly functions provided by viruses from several alternative genera and families, including vesiculovirus, flavivirus, and hepacivirus amongst others. This compatibility allows efficient egress in the extracellular milieu of co-infected cells of HDV particles that appear to be infectious. This leads to their subsequent entry into different cell types expressing the receptors targeted by the GPs of either virus genus and dissemination of HDV genome in vivo in infected humanized mice.

Overall, that unconventional cell transmission of HDV is experimentally possible in vivo raises the possibility that in nature, HDV could be associated with different virus types, including human viral pathogens, which could possibly favor previously unappreciated HDV transmission scenarios and modulate their pathogenicity.

HDV particles generated with heterologous envelope glycoproteins are infectious.
HDV particles generated with heterologous envelope glycoproteins are infectious. (a) Secretion and infectivity of delta particles (∆p) co-expressed with HBV GPs (designated “HDV”) or with surface GPs of the indicated viruses. As control, HDV was expressed without GPs (referred to as “No GP”), which provides baselines of HDV RNA RTqPCR analyses in producer Huh-7 cell supernatants (black bars) or in inoculated susceptible cells (red bars). The results are expressed per mL of cell supernatants or of cell lysates containing 106 cells. (b) Electron microscopy of the indicated heparin bead-purified ∆p particles as examined by electron microscopy samples after elution and negative staining. Note the presence of large (white arrows) and small (black arrows) particles. Scale bar (lower left): 100 nm.

Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo. Perez-Vargas, J., F. Amirache, C. Mialon, B. Boson, N. Freitas, C. Sureau., F. Fusil and F.-L. Cosset (2019). Nature Communications. May 8, 2019. doi: 10.1038/s41467-019-10117-z

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