Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease.

Gabriel Westman,Shaman Muradrasoli,Martin Ingelsson,Josef D Järhult,Catherine Schoofs,Nancy M Sawtell

doi:10.1371/journal.pone.0227670

Gabriel Westman, Shaman Muradrasoli + Show 4 more

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https://doi.org/10.1371/journal.pone.0227670

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Journal: PloS one	Publication Date: Jan 9, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Uppsala University, Karolinska Institutet

Abstract

Torque teno virus (TTV) is an unenveloped, circular, single stranded DNA virus with a genome size of approximately 3.8 kb. Previous studies have demonstrated varying grades of association between TTV DNA levels and immune deficiencies related to age, chronic infections and cancer. Alzheimer's disease (AD) has been related to persistent viral infections such as HSV-1 and CMV, but it is not known whether TTV viral load could serve as a functional biomarker of cellular immunity in this setting. Therefore, the objective of this study was to investigate whether TTV infection and viral load is related to AD status, CMV immunity, systemic inflammation or HLA types connected to anti-viral immunity. A total of 50 AD subjects and 51 non-demented controls were included in the study. AD subjects were diagnosed according to NINCDS-ADRDA and DSM-IV criteria and neuroradiologic findings were consistent with the diagnosis. TTV viral load was analyzed in plasma samples using a quantitative real-time PCR. Using a cut-off for TTV status at 200 copies/ml, 88% (89/101) of the study subjects were classified as TTV positive. TTV viral load significantly increased with age (beta 0.049 per year, p<0.001) but significantly decreased in relation to CMV IgG levels (beta -0.022 per 1000 units, p = 0.005) and HLA-B27 positivity (beta -0.53, p = 0.023). In conclusion, TTV immune control is not significantly affected by AD status, but appears related to age, CMV humoral immune response and HLA type.

Highlights

Torque teno virus (TTV) is an unenveloped, circular and single stranded DNA virus with a genome size of approximately 3.8 kb [1]
Our finding of 88% of subjects being TTV DNA positive is in line with previous studies, describing a TTV DNAemia prevalence in the general population ranging between 68 and Alzheimer’s disease (AD) status Sex Age CMV serostatus CMV IgG (1000 units) HLA-B27 HLA-B57 ApoE4 CRP IL-6
In most studies where TTV DNA have been quantified by real-time PCR, the viral load was in the range of 1×102 copies/ml to 1×106 copies/ml, which is in agreement with our results

Summary

Introduction

Torque teno virus (TTV) is an unenveloped, circular and single stranded DNA virus with a genome size of approximately 3.8 kb [1]. The virus, belonging to the Anelloviridae family, was first identified in 1997 in the serum of a Japanese patient who suffered from post-transfusion hepatitis [2]. A total of 29 TTV genotypes have been determined and classified in the genus Alphatorquevirus [3]. TTV DNA is detectable in 70 to 90 percent of the human population and viral load is usually in the range of 3–6 log copies/ml [4]. TTV infection has not been shown to cause clinical disease, but the virus has been associated with many viral co-infections such.

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