Adaptive evolution of simian immunodeficiency viruses isolated from 2 conventional-progressor macaques with...

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Simian immunodeficiency virus (SIV) infection in macaques can lead to encephalitis, particularly in rapidly progressing cases.
• Encephalitis is a less common but significant complication in conventional SIV disease progression.

Purpose of the Study:

• To analyze viral characteristics in two conventional SIV-infected macaques that developed encephalitis.
• To investigate viral evolution, compartmentalization, and adaptation within the central nervous system (CNS) and periphery.

Main Methods:

• Phylogenetic analysis of SIV isolates from cerebrospinal fluid (CSF) and plasma.
• Analysis of viral adaptive evolution in specific cell types (monocyte-derived macrophages and peripheral blood mononuclear cells).
• Examination of N-linked glycosylation sites in glycoprotein 160 (gp160) from CNS-derived viruses.

Main Results:

• Phylogenetic analyses revealed distinct viral populations (compartmentalization) in the CSF and plasma of both macaques.
• SIV isolates demonstrated adaptive evolution, with preferential replication in their respective cellular targets.
• A statistically significant reduction in potential N-linked glycosylation sites was found in gp160 from viruses within the CNS.

Conclusions:

• SIV encephalitis in conventional progressors involves viral compartmentalization and adaptive evolution.
• The virus adapts to replicate in specific host cells, including those within the CNS.
• Alterations in viral envelope glycoproteins, such as gp160, may play a role in CNS adaptation and pathogenesis.