Coreceptor usage of sequential isolates from cynomolgus monkeys experimentally Infected with simian immunodeficiency...

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Simian immunodeficiency virus (SIVsm) is a lentivirus related to HIV.
• Coreceptors like CCR5 and CXCR4 are crucial for viral entry into host cells.
• Understanding SIVsm coreceptor tropism is vital for studying lentiviral pathogenesis.

Purpose of the Study:

• To investigate the coreceptor usage of sequential SIVsm isolates from experimentally infected cynomolgus monkeys.
• To determine the stability and dynamics of SIVsm coreceptor tropism over time during infection.
• To identify potential shifts in coreceptor use that may influence viral replication and disease progression.

Main Methods:

• Sequential SIVsm isolates from infected cynomolgus monkeys were analyzed.
• Coreceptor usage was assessed using the GHOST(3) indicator cell line expressing CD4 and various chemokine receptors (CCR3, CCR5, CXCR4, BOB, Bonzo).
• Viral infection efficiency was quantified by measuring green fluorescence protein expression via flow cytometry.

Main Results:

• All SIVsm inoculum viruses and early reisolates efficiently used CCR5.
• CCR5 usage remained stable throughout the infection course.
• Late-stage isolates showed variable coreceptor use, with reduced efficiency for BOB and Bonzo, and sometimes failed to infect cells expressing these receptors.
• Unexpectedly, early reisolates (12 days post-infection) infected the entire GHOST(3) panel, including parental cells, in one case due to CXCR4 usage.

Conclusions:

• SIVsm isolates exhibit complex coreceptor usage patterns.
• CCR5 is the primary and stable coreceptor for SIVsm.
• Early viral replication is characterized by broader coreceptor availability, potentially influencing the initial infection pattern.
• Coreceptor availability in the early phase of infection may dictate the virus's replication strategy.