Human Mannose Receptor 1 Attenuates HIV-1 Infectivity in a Virus Isolate-Specific Manner.

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Human mannose receptor 1 (hMRC1) is a macrophage C-type lectin involved in HIV-1 binding and uptake.
• Previous studies identified hMRC1 as an antiviral factor inhibiting HIV-1 release via a BST-2-like mechanism, independent of virus isolate and Env.
• This study investigates a second, distinct antiviral function of hMRC1 impacting viral particle infectivity.

Purpose of the Study:

• To characterize a novel antiviral function of hMRC1 that inhibits HIV-1 infectivity.
• To identify the viral determinants responsible for hMRC1-mediated inhibition of infectivity.
• To explore the interaction between hMRC1 and HIV-1 Env proteins.

Main Methods:

• Analysis of chimeric HIV-1 Env proteins to determine inhibitory determinants.
• Co-immunoprecipitation assays to study hMRC1 and Env interactions.
• Assessment of hMRC1 inhibition on various HIV-1 isolates, including Transmitted/Founder (T/F) viruses.

Main Results:

• hMRC1 inhibits HIV-1 infectivity in a virus isolate-specific manner, contrasting with its effect on virus release.
• The Env V3 region is a critical determinant for hMRC1-mediated inhibition of viral infectivity.
• hMRC1 interacts strongly with sensitive HIV-1 Env (NL43) but poorly with resistant Envs (AD8, 49.5).
• Over half of tested R5-tropic T/F viruses were inhibited by hMRC1.

Conclusions:

• hMRC1 possesses a second antiviral mechanism targeting HIV-1 infectivity, dependent on the Env V3 region.
• hMRC1 packaging into virions is Env-independent.
• The interaction between hMRC1 and Env, particularly the V3 region, is crucial for inhibiting viral infectivity, potentially by hindering coreceptor binding.