HIV-1 evolves into a nonsyncytium-inducing virus upon prolonged culture in vitro

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) is a syncytium-inducing (SI) virus with a broad host cell range.
• A previously isolated LAI variant showed improved replication in SupT1 T cells due to mutations in the Env protein's C1 and C4 regions.

Purpose of the Study:

• To investigate the host cell range and Env-mediated functions of an HIV-1 LAI variant adapted to SupT1 cells.
• To understand the mechanistic basis for the selective adaptation and altered tropism of the HIV-1 variant.

Main Methods:

• Analysis of Env-mediated functions including coreceptor usage, Env glycoprotein biosynthesis, intracellular processing, and infectivity.
• Comparison of viral replication, virus production, and syncytia formation between the wild-type LAI virus and the Env-mutated variant in various cell types.

Main Results:

• The HIV-1 variant exhibited a severely restricted host cell range, with abolished replication in most tested T cell lines and primary cells.
• The altered tropism was not due to a switch to a SupT1-specific coreceptor or improved Env biosynthesis/processing in SupT1 cells.
• The variant showed a dramatic loss of infectivity in non-SupT1 cells but achieved approximately fivefold higher virus production in SupT1 cells, without inducing syncytia.

Conclusions:

• The HIV-1 variant's adaptation to SupT1 cells resulted in a shift from a syncytium-inducing (SI) to a nonsyncytium-inducing (NSI) phenotype.
• This evolution favors prolonged host cell survival and increased viral progeny, suggesting a balance between replication and host cell viability.
• The findings challenge the notion of a unidirectional NSI to SI evolution in HIV-1 and may explain the absence of SI variants in early infection stages.