A Single-Nucleotide Polymorphism of αVβ₃ Integrin Is Associated with the Andes Virus Infection Susceptibility.

Constanza Martínez-Valdebenito,Marcela Ferrés,Gregory Mertz,Cecilia Vial,Pablo Vial,Nicole Le Corre,Jenniffer Angulo,Jaime Cerda,Juan Miquel,Claudia Marco,Marcelo Lopez-Lastra

doi:10.3390/v11020169

Constanza Martínez-Valdebenito, Marcela Ferrés + Show 9 more

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https://doi.org/10.3390/v11020169

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Abstract

The Andes Orthohantavirus (ANDV), which causes the hantavirus cardiopulmonary syndrome, enters cells via integrins, and a change from leucine to proline at residue 33 in the PSI domain (L33P), impairs ANDV recognition. We assessed the association between this human polymorphism and ANDV infection. We defined susceptible and protective genotypes as “TT” (coding leucine) and “CC” (coding proline), respectively. TT was present at a rate of 89.2% (66/74) among the first cohort of ANDV cases and at 60% (63/105) among exposed close-household contacts, who remained uninfected (p < 0.05). The protective genotype (CC) was absent in all 85 ANDV cases, in both cohorts, and was present at 11.4% of the exposed close-household contacts who remained uninfected. Logistic regression modeling for risk of infection had an OR of 6.2–12.6 (p < 0.05) in the presence of TT and well-known ANDV risk activities. Moreover, an OR of 7.3 was obtained when the TT condition was analyzed for two groups exposed to the same environmental risk. Host genetic background was found to have an important role in ANDV infection susceptibility, in the studied population.

Highlights

Hantaviruses, members of the Hantaviridae family, genus Orthohantavirus, are the etiological agents of two zoonotic diseases, known as hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) [1,2]
Recent studies have linked the severity of Andes Orthohantavirus (ANDV) infections to genetic factors
We sought to address whether the risk of infection may be associated with host variants, as an association between single nucleotide polymorphism (SNP) rs5918 and ANDV infection has been suggested by in vitro studies [14,20]

Summary

Introduction

Hantaviruses, members of the Hantaviridae family, genus Orthohantavirus, are the etiological agents of two zoonotic diseases, known as hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) [1,2]. Andes hantavirus (ANDV) is the sole etiological agent of HCPS in Chile and Southern Argentina, and its main reservoir is the long-tailed pygmy. Through 14 July 2018, a total of 1141 cases of ANDV have been reported in Chile, with a lethality of 30% to 35% [5]. Transmission of ANDV to humans occurs mainly by exposure to aerosolized feces, urine, and saliva of infected rodents. ANDV person-to-person transmission has been reported in Chile and Argentina [5,6,7]. After environmental or interpersonal virus exposure, the incubation period for ANDV infections has been estimated to be between 7 to 39 days, with an average of 18 days [6,8], while in the 2012

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