Molecular characterization of an attenuated human immunodeficiency virus type 2 isolate

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Naturally occurring strains of human immunodeficiency virus (HIV) exhibit diverse in vitro biological properties that may influence in vivo pathogenesis.
• Understanding the genetic basis of viral pathogenicity is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To define the genetic determinants of viral pathogenicity in an attenuated strain of HIV type 2 (HIV-2/ST).
• To investigate the role of specific mutations in the envelope fusion region of HIV-2/ST in its non-fusogenic and non-cytopathic phenotype.

Main Methods:

• Molecular cloning and sequencing of an attenuated HIV-2/ST isolate (HIV-2/ST) and its proviral clone (JSP4-27).
• Analysis of nucleotide and amino acid sequences, focusing on the envelope fusion region.
• Amplification, cloning, and sequencing of the envelope fusion regions of additional HIV-2/ST strains, including in vitro-generated variants.

Main Results:

• The proviral clone JSP4-27 fully exhibited the non-cytopathic and non-fusogenic properties of its parental isolate.
• Sequence analysis revealed two amino acid substitutions in the envelope fusion region of JSP4-27 compared to prototype HIV-2 strains.
• All examined HIV-2/ST strains, including fusogenic variants, possessed the same amino acid sequence changes in the envelope fusion domain.

Conclusions:

• The attenuated phenotype of HIV-2/ST and JSP4-27 is not caused by direct alterations in the envelope fusion domain.
• This study demonstrates for the first time that replication-competent proviral clones can accurately represent attenuated HIV strains.
• The findings suggest that other genetic factors contribute to the attenuated pathogenicity of this HIV-2 strain.