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

EBioMedicine(2019)

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摘要
Abstract Background 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. Methods 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. Findings 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 BST2 : p 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. Interpretation 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.
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关键词
Restriction factors,HIV-1 infection,Cohorts,LTNP,Early treatment
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