Incompletely closed HIV-1_CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating...

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• HIV-1 envelope glycoproteins (Envs) are critical for viral entry and the primary targets of neutralizing antibodies.
• Envs must balance antibody evasion with maintaining entry efficiency.
• Transmitted/founder Envs often exhibit resistance to broadly neutralizing antibodies (bnAbs).

Purpose of the Study:

• To investigate the viral entry efficiency, fitness, and replication of the incompletely closed, transmitted/founder HIV-1 Env CH040.
• To determine if high resistance to bnAbs impacts viral entry efficiency.
• To understand the relationship between bnAb resistance and HIV-1 entry.

Main Methods:

• Studied the entry efficiency, fitness, and replication of CH040 HIV-1 Envs.
• Compared CH040 Env entry efficiency to other primary Envs.
• Engineered CH040 variants to increase bnAb resistance.
• Assessed in vitro spread of SHIV CH040 in macaque lymphocytes.

Main Results:

• CH040 Envs mediated HIV-1 entry as efficiently as other primary Envs.
• Antibody resistance and efficient viral entry appear to develop independently.
• Engineered CH040 variants with increased bnAb resistance showed no significant decrease in entry efficiency.
• Robust in vitro spread of SHIV CH040 was observed, comparable to other SHIVs.

Conclusions:

• HIV-1 Env antibody resistance can coexist with efficient viral entry.
• The findings suggest that resistance to bnAbs does not necessarily impair viral entry.
• This research provides crucial insights into the evolutionary strategies of HIV-1 for immune evasion and host cell entry.