HeLa cells: control vs IFN-gamma-treated

ABSTRACT: Transcriptional profiling of HeLa cells comparing control untreated HeLa cells with IFN-gamma-treated HeLa cells To infect host cells, many viruses use small cellular compartments, called endosomes, for entry, and the thiol/disulfide interchange in viral envelope glycoproteins (Envs) is crucial for infection. By screening cysteine-reacting chemicals, we found a compound, 4,4’-dithiopyridine, which is active at acidic pH, efficiently restricts retrovirus vector infection. We thus hypothesized that some products of endosome-localized, interferon-stimulated genes (ISGs) exhibit anti-viral activity by inhibiting thiol/disulfide interchange in viral Envs. Among the hundreds of ISGs, gamma-interferon (IFN)-inducible lysosomal thiolreductase (GILT) is the only molecule that resides in the endosomes/lysosomes and digests the S-S bonds of proteins under acidic conditions. We now report that GILT significantly inhibits the replication of retroviruses, including HIV-1 and MLV, by restricting both the early and late phases of their life cycles. Using the VSV-G pseudotyped HIV-1 model, we found that GILT digests the S-S bonds of viral Env proteins. GILT also inhibits HIV-1 viral release by digesting the S-S bond of CD63, an endosome-localized molecule reportedly involved in HIV-1 particle release. The effect of -IFN on HIV-1 is limited, although GILT induced by gamma-IFN is supposed to have anti-HIV-1 activity. We found that while gamma-IFN effectively inhibits MLV replication through GILT, the gamma-IFN signaling is remarkably inhibited by the HIV-1 Env protein, but not the MLV Env protein. These findings suggest that GILT functions as an anti-viral host factor induced by gamma-IFN, however, HIV-1 may have evolved to inhibit gamma-IFN signaling by the Env protein.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79568 | GEO | 2017/01/01

SECONDARY ACCESSION(S): PRJNA316194

REPOSITORIES: GEO