Potential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIV

Area of Science:

• Virology
• Human Genetics
• Reproductive Biology

Background:

• Viruses have historically integrated into the human germ line, contributing to human genome evolution.
• Several contemporary viruses, including human immunodeficiency virus (HIV), infect the human testis.

Purpose of the Study:

• To investigate if human testicular germ cells (TGCs) can support HIV integration.
• To explore the potential for HIV to become an endogenous retrovirus in the human germ line.

Main Methods:

• In vitro infection assays using isolated primary TGCs and a spermatogonial cell line.
• Cell-associated infection models involving HIV-infected lymphocytes.
• In vivo detection of viral DNA in TGCs using DNAscope.
• Molecular landscape analysis of TGCs' cellular environment and antiviral defenses.

Main Results:

• Isolated TGCs bind HIV-1 via alternative receptors but do not support viral entry in vitro.
• Cell-associated infection allows HIV-1 entry, integration, and early protein expression in TGCs.
• HIV-1 and simian immunodeficiency virus (SIV) DNA detected in a few TGCs in vivo.
• TGCs exhibit low antiviral defenses and are enriched in HIV early cofactors compared to other testicular cells.

Conclusions:

• Human TGCs can support HIV entry and integration, particularly through cell-associated infection.
• This interaction presents a potential mechanism for HIV to integrate into the human germ line.
• The findings suggest a possible future endogenization of HIV, mirroring historical viral integration events.