Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian...

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Primate lentiviruses, including HIV-1 and SIV, utilize CD4 and chemokine receptors like CCR5 for cell entry.
• While CCR5 is a known coreceptor for SIV, other cellular receptors remain unidentified.
• HIV-1 can utilize alternative chemokine receptors, particularly in the central nervous system or during disease progression.

Purpose of the Study:

• To identify novel coreceptors for Simian Immunodeficiency Viruses (SIV).
• To investigate the expression of potential SIV coreceptors in human and non-human primate immune cells.

Main Methods:

• Screening of orphan seven-transmembrane segment receptors for SIV coreceptor activity.
• Analysis of receptor expression in human alveolar macrophages, CD4(+) T lymphocytes, and rhesus macaque peripheral blood mononuclear cells.

Main Results:

• Two orphan seven-transmembrane segment receptors, gpr1 and gpr15, were identified as functional coreceptors for SIV.
• Gpr15 demonstrated efficient coreceptor activity and was expressed in human CD4(+) T lymphocytes and activated rhesus macaque cells.
• Gpr1 and gpr15 share structural similarities with CCR5, including a tyrosine-rich amino-terminal motif, despite lacking other chemokine receptor hallmarks.

Conclusions:

• Gpr1 and gpr15 represent novel coreceptors for SIV, expanding the known repertoire of viral entry cofactors.
• The findings highlight the potential diversity of seven-transmembrane receptors used by primate lentiviruses.
• Understanding these diverse entry pathways can contribute to insights into viral variation and pathogenesis.