Infection of macaques with an R5-tropic SHIV bearing a chimeric envelope carrying subtype E V3 loop among subtype B...

Area of Science:

• * Virology and retrovirology research.
• * Development of simian/human immunodeficiency virus (SHIV) models for studying HIV-1 pathogenesis.
• * Immunology and vaccine development strategies.

Background:

• * Simian/human immunodeficiency virus (SHIV) is a valuable tool for studying human immunodeficiency virus (HIV) infection and developing interventions.
• * The envelope protein's V3 loop plays a critical role in viral tropism and coreceptor usage (CCR5/CXCR4).
• * Understanding how envelope modifications affect viral replication and pathogenesis is crucial for developing effective therapies and vaccines.

Purpose of the Study:

• * To engineer a novel SHIV clone (SHIV-TH09V3) by incorporating subtype E V3 loop sequences into a subtype B SHIV backbone.
• * To evaluate the replication capacity and infectivity of the chimeric SHIV in various macaque models.
• * To determine the coreceptor usage and tropism of the engineered SHIV and its impact on viral pathogenesis.

Main Methods:

• * Genetic engineering of SHIV(MD14) to create chimeric virus SHIV-TH09V3 with subtype E V3 loops.
• * Propagation of SHIV-TH09V3 in peripheral blood mononuclear cells (PBMCs) from pig-tailed and cynomolgus macaques.
• * Inoculation of macaques with SHIV-TH09V3 and assessment of viral load, virus isolation, antibody production, and coreceptor usage via GHOST cell assay.

Main Results:

• * SHIV-TH09V3 successfully replicated in human and macaque PBMCs and infected both pig-tailed and cynomolgus macaques.
• * Infected macaques exhibited plasma RNA viremia, virus isolation from PBMCs and plasma, and developed antibodies against viral proteins.
• * SHIV-TH09V3 consistently displayed an R5-tropic phenotype, unlike the dual-tropic parental SHIV(MD14), indicating the V3 loop's role in tropism determination.

Conclusions:

• * The engineered SHIV-TH09V3 clone is capable of infecting macaques and retains an R5-tropic phenotype, governed by the subtype E V3 loop.
• * This chimeric virus serves as a valuable model for investigating the role of V3 loop sequences in SHIV pathogenesis and coreceptor tropism.
• * Future studies will compare the pathogenic outcomes of SHIV-TH09V3 and SHIV(MD14) in macaques to elucidate the impact of V3 sequence variations on disease progression.