Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever, for which there are limited treatment options. Successful LASV entry requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of GP1 mutant proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus residue (L84N, K88E, L10F, and H170S) reduced the binding affinity of GP1LASV for LAMP1. Moreover, all the mutations caused decreases in GPC-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, whereas L107F and H170S had only mild effects on infectivity. Notably, in LAMP1 knockout cells, all four mutants showed reduced pseudovirus infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order L84N > L107F > K88E > H170S.

IMPORTANCELassa virus requires pH-dependent receptor switch to infect host cells; however, the underlying molecular mechanisms of this process are not well known. Here, we identify four residues, L84, K88, L107, and H170 that contribute to the interaction with the second receptor lysosome-associated membrane protein 1 (LAMP1). Mutant any of the four residues would impair the binding affinity to LAMP1, decrease the glycoprotein mediated membrane fusion, and reduce the pseudovirus infectivity.
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The categories of this paper are: molecular
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The categories of this paper are: physiology
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The categories of this paper are: bioinformatics
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The categories of this paper are: ecology
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The categories of this paper are: pathology
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The categories of this paper are: immunology
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The categories of this paper are: cell
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The categories of this paper are: pharmacology
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The categories of this paper are: synthetic
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The categories of this paper are: biochemistry
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The categories of this paper are: neuroscience
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The categories of this paper are: developmental
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The categories of this paper are: paleontology
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The categories of this paper are: cognition
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The categories of this paper are: evolutionary
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The categories of this paper are: scientific