Early treated HIV-1 positive individuals demonstrate similar restriction factor expression profile as long-term non-progressors

• Published in: EBioMedicine Vol. 41; pp. 443 - 454
• Main Authors: Van Hecke, Clarissa, Trypsteen, Wim, Malatinkova, Eva, De Spiegelaere, Ward, Vervisch, Karen, Rutsaert, Sofie, Kinloch-de Loes, Sabine, Sips, Magdalena, Vandekerckhove, Linos
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019; Elsevier
• Subjects: Adult; Advanced Basic Science; Antiretroviral Therapy, Highly Active; Biomarkers; CD4 Lymphocyte Count; Cohorts; Disease Progression; Early treatment; Female; Gene Expression Profiling; Gene Expression Regulation; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV Seropositivity; HIV-1; HIV-1 infection; Host-Pathogen Interactions - genetics; Humans; Internal Medicine; LTNP; Male; Middle Aged; Phenotype; Research paper; Restriction factors; Time-to-Treatment; Viral Load; Virus Replication; LTNP; HIV-1 infection; Early treatment; Restriction factors; Cohorts
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2019.02.006

A wide range of host restriction factors (RF) become upregulated upon HIV-1 infection to suppress viral infectivity and may aid viremic control in vivo. This cross-sectional study evaluated HIV-1 RFs and dependency factors in HIV infected individuals with progressive or non-progressive infection, as well as in early and late treated cohorts that exhibit different viro-immunological profiles due to differences in timing of treatment-initiation. The expression profile of IFIT1, MX1, APOBEC3G, SAMHD1, BST2 (encoding TETHERIN), TRIM5, MX2, SLFN11, PAF1, PSIP1 (encoding LEDGF/p75), and NLRX1 was measured by qPCR in 104 HIV-1 positive individuals: seroconverters (SRCV; n = 19), long term non-progressors (LTNP; n = 17), viremic progressors (VP; n = 12), patients treated during seroconversion (Early treated; n = 24) or chronic infection (Late treated; n = 32), and non-infected controls. Expression levels of early treated HIV-1 positive individuals were significantly upregulated in comparison to late treated patients (IFIT1: p = 0·0003; MX1: p = 0·008; APOBEC3G: p = 0·002; SAMHD1: p = 0·0008; SLFN11: p < 0·0001; BST2: p < 0·0001). Similarly, SLFN11, BST2, and SAMHD1 were highly expressed in LTNPs at comparable levels as in early treated HIV-1 positive individuals. Furthermore, SLFN11 and SAMHD1 expression negatively correlated with total and integrated HIV-1 DNA levels. Early treatment initiation maintains initial RF elevation even after a decade of ART. Elevated expression of SLFN11, BST2, and SAMHD1 in LTNP and early treated subjects implies that these RFs may be associated with spontaneous virological control.