Urinary ß2-microglobulin as an early marker of infantile enterovirus and human parechovirus infections.

Enterovirus and human parechovirus (HPeV) are RNA viruses belonging to the family Picornaviridae that frequently infect infants. These infections show a wide variety of clinical manifestations, from mild to severe. However, there are no known early clinical markers for diagnosis and prediction of disease severity. The aim of this study was to examine the clinical utility of urinary beta 2-microglobulin (ß2MG) for the early detection and prognosis of infantile enterovirus and HPeV infections.This retrospective study included 108 full-term infants younger than 60 days of age, including 15 with enterovirus or HPeV-3 (enterovirus/HPeV-3), 22 with respiratory syncytial virus (RSV), and 24 with bacterial infections. Laboratory data and clinical characteristics were compared among these 3 groups. Of the 15 patients with enterovirus/HPeV-3, 6 were treated with intravenous immunoglobulin (IVIG subgroup) because of severe clinical conditions.Urinary ß2MG to creatinine ratio (ß2MG/Cr) was significantly higher in the enterovirus/HPeV-3 group compared to bacterial and RSV infection groups (both P < .001). In the enterovirus/HPeV-3 group, mean peak urinary ß2MG/Cr was observed on day 1 or 2. Urinary ß2MG/Cr values were significantly higher in the IVIG subgroup than the non-IVIG subgroup (P < .001).Increased urinary ß2MG/Cr in early-stage infection may be a useful clinical marker for the detection and prediction of infantile enterovirus and HPeV infection severity.

Viral-host interaction in kidney reveals strategies to escape host immunity and persistently shed virus to the urine.

Hepatitis A virus is one of five types of hepatotropic viruses that cause human liver disease. A similar liver disease is also identified in ducks caused by Duck Hepatitis A virus (DHAV). Notably, many types of hepatotropic viruses can be detected in urine. However, how those viruses enter into the urine is largely unexplored. To elucidate the potential mechanism, we used the avian hepatotropic virus to investigate replication strategies and immune responses in kidney until 280 days after infection. Immunohistochemistry and qPCR were used to detect viral distribution and copies in the kidney. Double staining of CD4+ or CD8+ T cells and virus and qPCR were used to investigate T cell immune responses and expression levels of cytokines. Histopathology was detected by standard HE staining. In this study, viruses were persistently located at scattered renal tubules. No CD4+ or CD8+ T cells were recruited to the kidney, which was only accompanied by transient cytokine storms. In conclusion, the extremely scattered infection was the viral strategy to escape host immunity and may persistently shed virus into urine. The deletion of Th or Tc cell responses and transient cytokine storms indeed provide an advantageous renal environment for their persistent survival.