Study of Andes virus entry and neutralization using a pseudovirion system

Area of Science:

• Virology
• Infectious Diseases
• Public Health

Background:

• Andes virus (ANDV) causes severe hantavirus pulmonary syndrome (HPS) with a 40% fatality rate.
• ANDV is unique among hantaviruses for its human-to-human transmission capability.
• Current research requires specialized high-containment facilities for studying ANDV.

Purpose of the Study:

• To develop a quantitative, high-throughput pseudovirion assay for Andes virus.
• To enable the study of ANDV infection and neutralization in biosafety level 2 (BSL-2) facilities.
• To investigate ANDV entry mechanisms, including pH dependency and receptor usage.

Main Methods:

• Constructed replication-defective vesicular stomatitis virus (VSV) pseudovirions incorporating ANDV glycoproteins.
• Replaced the VSV G protein gene with Renilla luciferase for quantifiable infection detection.
• Validated the assay by comparing neutralization titers with traditional plaque reduction neutralization tests (PRNT).

Main Results:

• The pseudovirion assay successfully quantified ANDV infection and neutralization.
• Demonstrated good concordance between the pseudovirion assay and PRNT for ANDV hamster sera.
• Utilized pseudovirions to explore ANDV entry requirements, such as pH and beta3 integrin.

Conclusions:

• The developed pseudovirion assay is a valuable tool for ANDV research in BSL-2 settings.
• This assay facilitates studying ANDV neutralization and infection dynamics.
• The assay aids in understanding the molecular mechanisms of ANDV entry into host cells.