Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection

Abstract

CD8+ cells from simian immunodeficiency virus (SIV)-infected long-term non-progressors and some uninfected macaques can suppress viral replication in vitro without killing the infected cells. The aim of this study was to identify factors responsible for non-cytolytic viral suppression by transcriptional profiling and to investigate their potential impact on SIV replication. Results of microarray experiments and further validation with cells from infected and uninfected macaques revealed that FAM26F RNA levels distinguished CD8+ cells of controllers and non-controllers (P=0.001). However, FAM26F was also expressed in CD4+ T-cells and B-cells. FAM26F expression increased in lymphocytes after in vitro IFN-γ treatment on average 40-fold, and ex vivo FAM26F RNA levels in peripheral blood mononuclear cells correlated with plasma IFN-γ but not with IFN-α. Baseline FAM26F expression appeared to be stable for months, albeit the individual expression levels varied up to tenfold. Investigating its role in SIV-infection revealed that FAM26F was upregulated after infection (P<0.0008), but did not directly correlate with viral load in contrast to MX1 and CXCL10. However, pre-infection levels of FAM26F correlated inversely with overall plasma viral load (AUC) during the acute and post-acute phases of infection (e.g. AUC weeks post infection 0–8; no AIDS vaccine: P<0.0001, Spearman rank correlation coefficient (rs)=−0.89, n=16; immunized with an AIDS vaccine: P=0.033, rs=−0.43; n=25). FAM26F transcript levels prior to infection can provide information about the pace and strength of the antiviral immune response during the early stage of infection. FAM26F expression represented, in our experiments, one of the earliest prognostic markers, and could supplement major histocompatibility complex (MHC)-typing to predict disease progression before SIV-infection.

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 + and CD8 + T-Cell Responses

“…Comparison of viral acquisition between the controls and 10 unvaccinated animals from another experiment infected with the same virus stock and dose by the same route showed that our challenge protocol yielded reproducible results (36). Inclusion of these historical controls in the calculations resulted in a reduction of the observed infection risk per exposure, relative to controls, of 75% for V2 (HR ϭ 0.248; 95% CI, 0.087 to 0.712; P ϭ 0.012).…”

“…IFN-␥ levels were significantly higher in V2 than in V1 (Mann-Whitney test; P ϭ 0.008) ( Fig. 7E) and correlated with the relative RNA levels of FAM26F and CXCL10 (FAM26F, r s ϭ 0.67, P Ͻ 0.0001 [36]; CXCL10, r s ϭ 0.69, P ϭ 0.015 [data not shown]). Surprisingly, in contrast to IFN-␥, plasma CXCL10 levels were significantly higher in V1 than in V2 (Mann-Whitney test; P ϭ 0.026 at 24 h and P ϭ 0.017 at 48 h) (Fig.…”

“…Relative RNA levels were quantified by real-time PCR using GAPDH as the reference gene. Primer sequencing for the amplification of GAPDH, CXCL10, MX1, BST-2, and FAM26F, as well as reverse transcription and PCRs, was performed as reported previously (36,86). Each sample was tested in triplicate using the ABI Prism 7500 system (PE Applied Biosystems).…”

Effect of oxidative stress and calcium deregulation on FAM26F (CALHM6) expression during hepatitis B virus infection

“…Various whole transcriptome analyses have demonstrated FAM26F to be differentially expressed in several viral (Simian Immunodeficiency Virus and Hepatitis C Virus (HCV)) [ 10 , 11 ], bacterial (Septicemic melioidosis, Staphylococcal Superantigens, and Staphylococcal Enterotoxin B) , [ 12 – 14 ], and parasitic infections like Gastrointestinal Nematode infection [ 15 ], in liver transplantation, and in several cancers (breast, mammary gland, cervix, and uterus) [ 16 ]. With respect to viral infections, FAM26F has only been studied in SIV [ 17 ] and HCV [ 11 ]. In SIV-infected Rhesus macaques, pre-infection levels of FAM26F were found to correlate with the overall viral load during the acute phase of infection, recognizing FAM26F as one of the earliest prognostic markers which can give information related to the pace and strength of antiviral immune response [ 17 ].…”

Unveiling the Physical and Functional Niches of FAM26F by Analyzing Its Subcellular Localization and Novel Interacting Partners

“… 3 Moreover, investigating its function in SIV infection showed that pre-infection levels of FAM26F correlate inversely with general viral load of plasma, and thus, FAM26F can be regarded as one of the earliest prognostic markers which, in the infection’s early stage, can give us information related to the pace and strength of antiviral’s immune response. 4 …”