Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea

Abstract

Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>108 copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections.

Human bocavirus 1 and 3 infection in children with acute gastroenteritis in Brazil

“…In Brazil, only three studies have been published regarding HBoV detection in children with acute gastroenteritis (Albuquerque et al 2007, Santos et al 2010, Proença-Modena et al 2011 and this is the first study conducted in the Central-West Region of Brazil. In addition, our study is unique because the study period of 1994-2004 allows us to assess HBoV-1 and HBoV-3 circulation prior to the discovery of this virus.…”

Frequency of human bocavirus respiratory infections among at-risk patients in São Paulo, Brazil

“…PROENÇA-MODENA et al (2011) used a quantitative PCR assay targeting the HBoV mRNA and described the probable HBoV pathogenicity in coinfections if higher mRNA loads occurred, probably indicating an active replication 18 . Another limitation was the long study period but we assumed that the collection of appropriate samples and appropriate storage could minimize possible bias.…”

Detección de bocavirus humano en la población infantil de Tucumán y Santa Fe, Argentina

“…Por este motivo, se debate si el virus causa infección respiratoria o es sólo un espectador de otras infecciones. No se encontró relación entre las coinfecciones y la aparición de enfermedad grave, al igual que en otras publicaciones 7,10,19 , en las que se describió que no existían diferencias significativas en la expresión clínica de los pacientes según estuvieran co-infectados o HBoV fuera el único agente detectado, en lo que respecta a signos y síntomas ni en el desarrollo de enfermedad grave.…”

“…El genoma de HBoV contiene tres marcos abiertos de lectura (en inglés open reading frames-ORFs). Los dos primeros codifican las proteínas no estructurales NS1 y NP1 y el tercero codifica las dos proteínas de la cápside viral: VP1 y VP2 9,10 . Cuatro especies de HBoV han sido descubiertas: HBoV1 es la especie que predomina en el árbol respiratorio mientras que HBoV2, HBoV3 y HBoV4 se hallaron principalmente en muestras de materia fecal 11 .…”

“…Sin embargo, HBoV tiene una elevada prevalencia en co-detecciones con otros patógenos 7,10,13,14,19,20,22 y se detectó en muestras de individuos asintomáticos 22,23,26 por lo cual aún debe ser confirmado su rol como patógeno.…”