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Discrete viral E2 lysine residues and scavenger receptor MARCO are required for clearance of circulating alphaviruses.

08:00 EDT 9th October 2019 | BioPortfolio

Summary of "Discrete viral E2 lysine residues and scavenger receptor MARCO are required for clearance of circulating alphaviruses."

The magnitude and duration of vertebrate viremia is a critical determinant of arbovirus transmission, geographic spread, and disease severity. We find that multiple alphaviruses, including chikungunya (CHIKV), Ross River (RRV), and o'nyong 'nyong (ONNV) viruses, are cleared from the circulation of mice by liver Kupffer cells, impeding viral dissemination. Clearance from the circulation was independent of natural antibodies or complement factor C3, and instead relied on scavenger receptor SR-A6 (MARCO). Remarkably, lysine to arginine substitutions at distinct residues within the E2 glycoproteins of CHIKV and ONNV (E2 K200R) as well as RRV (E2 K251R) allowed for escape from clearance and enhanced viremia and dissemination. Mutational analysis revealed that viral clearance from the circulation is strictly dependent on the presence of lysine at these positions. These findings reveal a previously unrecognized innate immune pathway that controls alphavirus viremia and dissemination in vertebrate hosts, ultimately influencing disease severity and likely transmission efficiency.

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This article was published in the following journal.

Name: eLife
ISSN: 2050-084X
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Medical and Biotech [MESH] Definitions

An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC 2.1.1.43.

Acetyltransferases that can transfer an acyl group to specific LYSINE residues within HISTONES (HISTONE ACETYLTRANSFERASES) and/or non-histone proteins.

Trans-acting transcription factors produced by retroviruses such as HIV. They are nuclear proteins whose expression is required for viral replication. The tat protein stimulates LONG TERMINAL REPEAT-driven RNA synthesis for both viral regulatory and viral structural proteins. tat stands for trans-activation of transcription.

Trans-acting nuclear proteins whose functional expression are required for retroviral replication. Specifically, the rev gene products are required for processing and translation of the gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion.

A family of scavenger receptors that mediate the influx of LIPIDS into MACROPHAGES and are involved in FOAM CELL formation.

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