Infectious Entry Pathway Mediated by the Human Endogenous Retrovirus K Envelope Protein

Journal of Virology
Lindsey R Robinson, Sean P J Whelan

Abstract

Endogenous retroviruses (ERVs), the majority of which exist as degraded remnants of ancient viruses, comprise approximately 8% of the human genome. The youngest human ERVs (HERVs) belong to the HERV-K(HML-2) subgroup and were endogenized within the past 1 million years. The viral envelope protein (ENV) facilitates the earliest events of endogenization (cellular attachment and entry), and here, we characterize the requirements for HERV-K ENV to mediate infectious cell entry. Cell-cell fusion assays indicate that a minimum of two events are required for fusion, proteolytic processing by furin-like proteases and exposure to acidic pH. We generated an infectious autonomously replicating recombinant vesicular stomatitis virus (VSV) in which the glycoprotein was replaced by HERV-K ENV. HERV-K ENV imparts an endocytic entry pathway that requires dynamin-mediated membrane scission and endosomal acidification but is distinct from clathrin-dependent or macropinocytic uptake pathways. The lack of impediments to the replication of the VSV core in eukaryotic cells allowed us to broadly survey the HERV-K ENV-dictated tropism. Unlike extant betaretroviral envelopes, which impart a narrow species tropism, we found that HERV-K ENV mediates broa...Continue Reading

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Citations

Aug 7, 2018·PLoS Pathogens·Lindsey R Robinson-McCarthySean P J Whelan
Oct 16, 2018·Critical Reviews in Microbiology·Marta Garcia-MontojoAvindra Nath
Apr 10, 2019·Nature Reviews. Microbiology·Welkin E Johnson
May 21, 2019·Frontiers in Microbiology·Yíngyún CaìJens H Kuhn
Jun 21, 2018·Frontiers in Microbiology·Krithika BhuvaneshwarYuriy Gusev

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