Characterization and titration of an HIV type 1 subtype E chimpanzee challenge stock

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Subtype E human immunodeficiency virus type 1 (HIV-1) E/90CR402 isolate from the Central African Republic.
• Need for a chimpanzee-adapted HIV-1 stock for vaccine studies.

Purpose of the Study:

• Adapt HIV-1 E/90CR402 to grow in chimpanzee peripheral blood mononuclear cells (PBMCs).
• Generate a chimpanzee challenge stock for HIV-1 vaccine research.

Main Methods:

• Cocultivation of irradiated, infected human PBMCs with chimpanzee PBMCs.
• Passaging the virus in chimpanzee PBMCs to create a stock.
• Demonstrating infectivity in chimpanzees via intravenous (i.v.) and cervical inoculation.
• Determining the i.v. infectious titer using TCID50.

Main Results:

• Chimpanzee-adapted virus showed a syncytium-inducing phenotype, unlike the parental non-syncytium-inducing virus.
• The adapted virus successfully infected chimpanzees via i.v. and cervical routes.
• The i.v. infectious titer was determined to be between 2 and 5 TCID50.

Conclusions:

• The HIV-1 E/90CR402 chimpanzee challenge stock establishes persistent infections in chimpanzees.
• This stock is valuable for future HIV-1 vaccine studies, particularly for evaluating cross-protection between subtypes.