Hantaan Virus RNA Load in Patients Having Hemorrhagic Fever With Renal Syndrome: Correlation With Disease Severity

Yi, Jun; Xu, Zhuwei; Zhuang, Ran; Wang, Jiuping; Zhang, Yusi; Ma, Ying; Liu, Bei; Zhang, Yun; Zhang, Chunmei; Yan, Guolin; Zhang, Fanglin; Xu, Zhihui; Yang, Angang; Jin, Boquan

doi:10.1093/infdis/jis475

Cited by 52 publications

(54 citation statements)

References 12 publications

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“…Our results clearly show that the HFRS incidence in China have decreased dramatically in during the last decade, which is similar to the general trend in several countries in Asia, as far back as 1920s to 1930s, China witnessed the prevalence of HFRS. The targeted vaccine development has lasted for decades since the isolation of the Hantaan virus at home and abroad in 1980 successively; after almost 20 years of efforts, multiple HFRS-targeted vaccines which have played an important role in the control of HFRS in China, have been developed2122. Currently, the prevention and treatment of HFRS in China follows the principle of “three-early and one-in-place”, namely, early discovery, early rest, early treatment and in-place isolation treatment, and it renders great progress in the prevention of HFRS, but it is still faced with challenges, with the implementation of NHFPC’s National HFRS monitoring program (Trial) since 2005, the disease incidence detected in most provinces showed significant decrease as in some previous studies2324.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

Huang

et al. 2016

Sci Rep

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Hemorrhagic fever with renal syndrome (HFRS) is one of the most common infectious diseases globally. With the most reported cases in the world, the epidemic characteristics are still remained unclear in China. This paper utilized the seasonal-trend decomposition (STL) method to analyze the periodicity and seasonality of the HFRS data, and used the exponential smoothing model (ETS) model to predict incidence cases from July to December 2016 by using the data from January 2006 to June 2016. Analytic results demonstrated a favorable trend of HFRS in China, and with obvious periodicity and seasonality, the peak of the annual reported cases in winter concentrated on November to January of the following year, and reported in May and June also constituted another peak in summer. Eventually, the ETS (M, N and A) model was adopted for fitting and forecasting, and the fitting results indicated high accuracy (Mean absolute percentage error (MAPE) = 13.12%). The forecasting results also demonstrated a gradual decreasing trend from July to December 2016, suggesting that control measures for hemorrhagic fever were effective in China. The STL model could be well performed in the seasonal analysis of HFRS in China, and ETS could be effectively used in the time series analysis of HFRS in China.

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Section: Discussionmentioning

confidence: 99%

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

Huang

et al. 2016

Sci Rep

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“…In our previous study, HTNV RNA could be detected in the plasma of HFRS patients only at 3 to 12 days after the onset of the disease, and the viral load gradually decreased to an undetectable level with the course of the disease, which is in accordance with the self-limiting properties of HFRS. There is a statistically significant association between plasma HTNV RNA load in the early stage and disease severity in patients, but there is no relationship between HTNV RNA load and the peak value of the titers of HTNV NP-specific IgM and IgG (17). Our previous studies also showed that the magnitude of the cellular immune response and the frequency of the epitope-specific pentamer-positive CD8 ϩ T cell response were much higher in patients with mild/moderate HFRS than in those with severe/critical disease at the acute stage of the disease.…”

Section: Discussionmentioning

confidence: 90%

CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

Liu

Yusi

et al. 2015

J Virol

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Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8؉ T cells play a critical role in combating HTNV infections. However, the contributions of different CD8 ؉ T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8 CD8 T cells play a critical role in combating viral infections. Dramatic cellular changes occur as T cells transition through the following three characteristic phases of an antiviral response: initial activation and expansion, the death phase, and the formation of memory T cells. However, many aspects of these activation and differentiation processes are inadequately understood, particularly in humans. There are several important cell surface molecules that regulate the interactions between immune cells and, moreover, characterize cell differentiation and activation status.Sema4D, also called CD100, was the first immune semaphorin discovered (1) and is involved in several aspects of both humoral and cellular immunity (2-6). CD100 exists in both a membranebound form and a soluble form. Membrane-associated CD100 is expressed preferentially on T cells and weakly on B cells and antigen-presenting cells (APCs) (2, 7). CD72, the receptor for CD100, is expressed primarily on immune system cells and is present on the surface of most APCs and B cells. Interaction between CD72 and CD100 leads to dendritic cell (DC) maturation and cytokine production and enhances B cell activation (7).Because of the involvement of CD100 in the immune response, we hypothesized that CD100 may play an important role in the antiviral CD8 T cell response. However, there is limited information available regarding the role of CD100 in infectious diseases. Eriksson et al. (8) investigated the effects of HIV-1 infection on CD100 expression in T cells, and they observed that a subset of CD8 ϩ T cells lacking membrane-associated CD100 showed decreased functional capacity. Their findings suggested that loss of CD100 expression would most likely lead to dysfunctional immunity in HIV-1 infection. It is well accepted that there are many differences between acute infections and chronic infections. Acute infections usually result in effective antiviral immune responses, while chronic infections are often associated with suboptimal T cell function. Furthermore, HIV infects CD4 ϩ T cells and B cells and has profound pathological effects on the immune system, further confounding the interpretation of T cell dynamics following the acute phase. Therefore, it is important to investigate the functional role of CD100 in the CD8 antiviral response in acute infections.

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“…However, no significant difference was found between the severe/critical group and the mild/moderate group (1894.31 ng/mL vs. 1957.78 ng/mL; p = 0.86, Figure 2E) in the oliguric stage. We also analyzed the relationship between plasma cf-DNA values in febrile/hypotensive stages and the viral load, which was reported to correlate positively with disease severity [2], and found that there is a significant positive correlation of plasma cf-DNA levels with viral load ( p ˂ 0.001, R = 0.68, Figure 2F).…”

Section: Resultsmentioning

confidence: 99%

“…Laboratory tests included blood platelets (×10 9 /L), serum creatinine level (μmol/L) and white blood cell count (×10 9 /L). The viral load data were also available from the study we had recently performed [2]. …”

Section: Methodsmentioning

confidence: 99%

“…HRFS clinical symptoms mainly include thrombocytopenia and, in severe cases, hemorrhage and capillary leakage. The pathogenesis of HFRS has been documented to some extent [2], but is still considerably far from being completely understood. Among all the well-known mechanisms underlying HFRS pathogenesis, immune response may play key roles, involving immune complexes, complement activation, B cell response, T cell response, and HTNV-induced cytokine production, which cause an increase of vascular permeability and tissue injury.…”

Section: Introductionmentioning

confidence: 99%

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Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load

Zhang

et al. 2014

Viruses

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Cell-free DNA (cf-DNA) in blood represents a promising DNA damage response triggered by virus infection or trauma, tumor, etc. Hantavirus primarily causes two diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS), depending on different Hantavirus species. The aim of this study was to evaluate plasma cf-DNA levels in acute phase of HFRS, and to correlate plasma cf-DNA with disease severity and plasma Hanttan virus (HTNV) load. We observed the appearance of cf-DNA in 166 plasma samples from 76 HFRS patients: the plasma cf-DNA levels peaked at the hypotensive stage of HFRS, and then decreased gradually. Until the diuretic stage, there was no significant difference in plasma cf-DNA level between patients and the healthy control. Exclusively in the febrile/hypotensive stage, the plasma cf-DNA levels of severe/critical patients were higher than those of the mild/moderate group. Moreover, the plasma cf-DNA value in the early stage of HFRS was correlated with HTNV load and disease severity. In most of the patients, plasma cf-DNA displayed a low-molecular weight appearance, corresponding to the size of apoptotic DNA. In conclusion, the plasma cf-DNA levels were dynamically elevated during HFRS, and correlated with disease severity, which suggests that plasma cf-DNA may be a potential biomarker for the pathogenesis and prognosis of HFRS.

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Hantaan Virus RNA Load in Patients Having Hemorrhagic Fever With Renal Syndrome: Correlation With Disease Severity

Cited by 52 publications

References 12 publications

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load

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Hantaan Virus RNA Load in Patients Having Hemorrhagic Fever With Renal Syndrome: Correlation With Disease Severity

Cited by 52 publications

References 12 publications

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

CD8lowCD100−T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection

Increased Plasma Cell-Free DNA Level during HTNV Infection: Correlation with Disease Severity and Virus Load

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CD8^lowCD100⁻T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection