Viral Diagnostics

Viral diagnostic methodology has advanced rapidly over recent years in terms of sensitivity and specificity. However, there continue to be considerable challenges in the diagnosis of viral infections in resource-limited regions. In the current issue of Viral Immunology, Harmon et al. point out that the advent of multiplex immunoassays has facilitated the study of biomarkers of disease since only small amounts of clinical material are required. However, such assays are only designed and validated for analyzing plasma or serum, which can be difficult to obtain in the field due to the need for additional processing of infectious materials. This is a significant impediment when studying emerging viruses such as the Ebola and Lassa Fever Viruses in the context of an outbreak in a low- or middle-income nation. To address this problem, the authors compared frozen and thawed human whole blood with frozen and thawed plasma from normal healthy donors in a series of multiplexed immunoassays for fifty-nine different biomarkers. Their data show that the most important biomarkers can be evaluated by using thawed whole blood. These findings will facilitate the study of human cytokine and other biomarker responses to viruses emerging in resource-limited regions. An example of an emerging viral infection is the Middle East respiratory syndrome coronavirus (MERS-CoV). This virus causes severe respiratory disease with significant mortality. Alhetheel and colleagues have investigated assays that are designed to detect MERS-CoV RNA or IgG in suspected and proven cases of MERS-CoV infection. Their data show that there was a lack of correlation between nucleic acid and serological analysis, indicating that MERS-CoV-IgG testing may not be suitable for diagnosing acute infection or estimating its prevalence during an outbreak. In addition, their data suggest that MERS-CoV-IgG may not have significant value in determining disease severity or prognosis.

An important use of viral diagnostics is to undertake epidemiological studies in vaccinated populations. In this regard, de Medeiros Nóbrega et al. evaluated the seropositivity of pregnant women to rubella virus after vaccination in Brazil. This is an important study because the rubella virus causes an acute viral disease that can cause serious abnormalities to fetuses in pregnant women; a syndrome referred to as Congenital Rubella Syndrome. Immunization against rubella was initiated in Brazil in 1992, but few epidemiological studies have been conducted to assess the program's success since then. In this study, the authors' data confirm high levels of vaccination coverage and anti-rubella immunization in Brazil's Federal District population.

The current issue of Viral Immunology features a review article by Ilyas and colleagues on the many extra-hepatic manifestations (EHMs) associated with hepatitis C virus (HCV) infections. EHMs affect many organ systems, including the heart, lungs, kidney, brain, thyroid, and skin. Further, HCV-related cardiac and pulmonary manifestations include myocarditis, cardiomyopathies, cardiovascular diseases, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and interstitial lung diseases. The review discusses the etiology and pathogenesis of HCV-associated diseases along with possible mechanisms.

Three additional papers cover different aspects of the host response to viral infections. Attatippaholkun and colleagues have investigated the complex interactions between dengue virus (DENV) and the blood coagulation system. The authors have developed a flow-cytometric approach to detect DENV and cell surface CD41a simultaneously. They further demonstrated that the approach could be modified for fluorescence microscopy to stain for CD41a on the cell surface and DENV intracellularly. Lu et al. point out that recently identified T memory stem cells (Tscm) have stem-cell-like properties, including long-lasting, self-renewal capacity, and multipotency to differentiate into other memory T cell types. They go on to demonstrate that CD4+ Tscm correlates with disease progression in chronically human immunodeficiency virus (HIV)-1-infected patients. This is an important finding since an abnormity of CD4+ Tscm cells may contribute to the pathogenesis and disease progression in HIV-1-infected individuals. Deng et al. discuss the fact that fowl aviadenoviruses (FAdVs) are distributed worldwide in poultry farms and cause inclusion body hepatitis and hydropericardium syndrome, with significant economic losses to the poultry industry. The authors show that the viral ORF1 protein plays a role in modulating the host immune response and subsequent replication of the virus. The study offers new insights into the mechanisms underlying the host immune response against FAdV infection.

Finally, I was an author on a hypothesis paper from Hurwitz et al. It is generally considered that viral sequence integration into the mammalian genome is a health risk. In this study, we propose that, comparable to the clustered regularly interspaced short palindromic repeats (CRISPR) that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory. We further hypothesize that host cells express viral peptides from open reading frames in integrated sequences to boost adaptive B cell and T cell responses long after replicating viruses are cleared. The commentary reviews current literature in the context of this new concept.

I would like to thank all the authors for their excellent contributions to the journal and all the volunteers and the reviewers for their help in maintaining the high quality of the published articles.