A novel method for distinguishing between dsDNA and ssRNA virus infections

doi:10.1016/j.jcv.2008.04.004

Journal of Clinical Virology

Volume 43, Issue 1, September 2008, Pages 49-55

https://doi.org/10.1016/j.jcv.2008.04.004 Get rights and content

Abstract

Background

To commence proper antiviral treatment, timely knowledge of whether the infection is caused by DNA or RNA virus would be beneficial for the clinician.

Objectives

Our objective was to develop a method for distinguishing between DNA and RNA virus infections.

Study design

In this prospective study, total and differential count of leukocytes, serum C-reactive protein level, erythrocyte sedimentation rate, and quantitative flow cytometric analysis of FcγRI (CD64) on neutrophils and monocytes were obtained from 289 hospitalized febrile patients. After microbiological confirmation, 89 patients (31%) were found to have either bacterial (n = 46) or viral (n = 43) infection. The patient data was compared to 60 healthy controls.

Results

For the first time ever, it was noticed that in dsDNA virus infections (n = 21) the average amount of CD64 on neutrophils was over five-fold compared to ssRNA virus infections (n = 22).

Conclusions

DNA virus score (DNAVS) point, which incorporates quantitative analysis of CD64 on neutrophils and total and differential count of leukocytes, varied between 0 and 8, and displayed 95% sensitivity and 100% specificity in distinguishing between dsDNA and ssRNA virus infections [average (S.D.); DNAVS points: 5.4 (2.5) vs. 0.3 (0.4); p < 0.001].

Introduction

Over the past few decades, several methods have been developed which help clinician to decide whether the infection is bacterial or viral in origin (Nuutila and Lilius, 2007a). However, so far, little attention has been paid to the development of a fast and reliable method(s) for differentiating between DNA and RNA virus infections.

We show here that in febrile double-stranded DNA (dsDNA) virus infections the average amounts of CD64 on neutrophils as well as total and differential counts of lymphocytes were significantly increased compared to febrile single-stranded RNA (ssRNA) virus infections, suggesting that these parameters are suited for distinguishing between DNA and RNA virus infections. An advantage of flow cytometric receptor analysis and automatic differential count of blood is rapidity. Notably, the time window from procuring the blood sample to data handling is less than 1 h.

Section snippets

Materials and methods

The local Ethical Committee of Turku University/Turku University Central Hospital approved the study protocol. Records were kept confidential according to official regulations.

CD64 on neutrophils and monocytes

The average number of CD64 on neutrophil surfaces was significantly at least five times higher in patients with bacterial and dsDNA virus infections than in patients with ssRNA virus infections, and insignificantly twice as high in RNA virus infections than in healthy controls (Table 1 and Fig. 2A). ROC curve analyses confirmed that the neutrophil CD64 was distinct between dsDNA and ssRNA virus infections, with at 90.5% sensitivity and 81.8% specificity (Table 2). Using isotype-matched control

Discussion

Reliably tested specific antiviral agents are available only for a few viral agents, e.g. nucleoside analogues for herpesviruses (Hewlett et al., 2004), neuraminidase inhibitors for influenza viruses (Jefferson et al., 2006), and antiretrovirals for HIV (Wainberg, 2004). To commence proper antiviral treatment as rapidly as possible, timely knowledge of whether the infection is caused by dsDNA or ssRNA virus would be beneficial for the clinician. For the first time ever, we present a specific

Acknowledgments

This study has been financially supported, in part, by National Technology Agency of Finland (Helsinki, Finland) and Turku University Hospital (Turku, Finland).

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