Human Bocavirus Infections Bocavirus Infections Ville Peltola, MD, Phd,* Maria Söderlund-Venermo, Phd,† and Tuomas Jartti, MD, Phd*

Divya J

INF ESPID Reports and Reviews 203075 Human Bocavirus Infections Bocavirus Infections Ville Peltola, MD, PhD,* Maria Söderlund-Venermo, PhD,† and Tuomas Jartti, MD, PhD*

Peltola et al n 2005, a previously unknown DNA virus HBoV1 has been detected for up to 6 is, therefore, not a sufficient evidence of an Iwas identified in nasopharyngeal specimens months in serial nasopharyngeal samples.11,12 acute HBoV1 infection and cannot be used from children with respiratory tract infec- Prolonged replication or passive persistence for estimating the clinical impact of this 1 XXX tion. Researchers used random polymerase may account for the frequent presence of virus. Recently, more solid data for the case chain reaction (PCR) amplification and high- HBoV1 in asymptomatic children. HBoV1 that HBoV1 can cause disease have been pro- throughput sequencing methods specifically often is present in samples together with vided by use of PCR in serum and by serol- developed for detection of unknown viral another respiratory virus, which might sug- ogy. In a study of wheezing children, 45 of Pediatr Infect Dis J sequences. Analysis of the recovered gene gest reactivation of a latent virus by a super- 49 (92%) with HBoV1 DNA in serum had sequences showed resemblance to bovine infection. However, there is no documented a serologic diagnosis as defined by posi- and canine minute parvoviruses, and the evidence of establishment of a persistent, tive IgM, IgG seroconversion or an >4-fold virus was named human bocavirus (HBoV). latent state by the HBoV. increase in IgG, whereas 2 of 15 children Lippincott Williams & Wilkins Later, 3 other HBoV were identified in stool (13%) with HBoV1 DNA only in their naso- 2,3 and named HBoV 2, 3 and 4. Disease asso- EPIDEMIOLOGY pharyngeal samples had serologically con- ciations of HBoV are not entirely clear, but 16 Globally the prevalence of HBoV1 firmed diagnoses. Hagerstown, MD recent studies provide evidence that HBoV1 DNA in young children with respiratory tract Studies using quantitative PCR and causes pneumonia and other respiratory tract infections is around 10%, in some studies serology associate bocavirus with wheezing diseases, in particular during primary infec- 4 illnesses and pneumonia. Only a few studies 4 up to 33%. It occurs year-round, but most tions. commonly in the winter. HBoV1 is more have used serum bocavirus PCR in a study frequently detected in young children (<2 setting with comparison groups without res- VIRUS STRUCTURE AND years of age) than in older children or adults. piratory tract infection. In one such study, BIOLOGICAL PROPERTIES Limited knowledge of transmission, persis- detection of HBoV1 DNA in serum was asso- tence, establishment of latency, reinfections ciated with lower respiratory tract illnesses HBoV is a small DNA virus with a and pneumonia.17A serological follow-up nonenveloped icosahedral capsid similar to and reactivations cause uncertainties regard- 5 ing the epidemiology of HBoV1. Of the study of 109 children from infancy to early other Parvoviridae. The 5 kb linear and sin- adolescence compared the clinical events gle-stranded genome is organized in 3 open enteric bocavirus types, HBoV2 is the most prevalent with detection rates of up to 26% during the sampling intervals when sero- reading frames that encode 2 forms of the conversion occurred with the next and prior nonstructural protein NS1, a nuclear phospho- in stool samples from children, and 4% from 2,3 intervals, and found an association between protein NP1, and 2 structural capsid proteins, adults. DNA of HBoV3 and HBoV4 has primary HBoV1 infection and respiratory VP1 and VP2.6 HBoV types 2–4 have similar been detected in <5% of stool samples. tract illnesses including acute otitis media.14 genomic organizations as HBoV1 and 10%– Seroepidemiologic studies have docu- Type 2 bocavirus has been detected in stool in 30% sequence dissimilarities.3 mented that most children have IgG antibod- 2013 ies against HBoV1 by school age.13,14 Dif- 3%–25% of children with gastroenteritis, but Replication mechanisms of HBoV ferentiation between seroresponses against often with another enteric virus.2,18,19 HBoV2 and the pathogenesis of HBoV infections are HBoV types 1 to 4 is, however, difficult has been found also in stool of healthy indi- poorly characterized. This is largely because because of cross-reactivity.15 viduals, and any association with gastroen- no animal model is available and tissue cul- teritis is weak. Taken together, there is sub- Copyright © 2013 Lippincott Williams & Wilkins ture of HBoV is difficult, although it has been stantial amount of data linking HBoV1 with cultured in primary respiratory epithelial CLINICAL MANIFESTATIONS upper and lower respiratory tract infections, cells.7 The primary replication site of HBoV1 Many studies have reported an asso- some data linking HBoV2 with gastroen- 0178 appears to be the respiratory tract, where it ciation between a respiratory tract infection teritis and very few data linking HBoV3 or has been detected most frequently and in and HBoV1 detected by PCR in the naso- HBoV4 with any clinical illness. Studies with highest copy numbers. HBoV1 can be found pharynx. Clinical manifestations have ranged robust diagnostic methods in controlled pop- 00 also in serum, pointing to a systemic spread.8,9 from mild upper respiratory tract infections ulations would be needed to increase knowl- Viral copy numbers of HBoV1 in stool are to severe pneumonia. However, because of edge of the clinical impact of bocavirus in low. On the contrary, HBoV types 2–4 have insufficient diagnostic methods, selected children and adults. 0891-3668 been detected predominantly in stool, but the patient populations and lack of control host cell types are not known.2,3,10 groups, the majority of studies are of limited value. The pathogenic role of HBoV1 has DIAGNOSIS 10.1097/INF.0b013e31827fef67 been challenged by documentation of other HBoV1 infections cannot be clinically From the *Department of Pediatrics, Turku Univer- viruses in the same samples (up to 90%) and differentiated from other viral respiratory sity Hospital and University of Turku, Turku; and infections. Bocavirus isolation in tissue cul- †Department of Virology, Haartman Institute, detection of bocavirus also in asymptomatic The Pediatric Infectious Disease Journal University of Helsinki, Helsinki, Finland. individuals (up to 44%).4 In a study of chil- ture is not available for diagnostic use. HBoV Supported by Academy of Finland (grant no. 140251). dren in day-care centers, 33% of those with can be readily detected by PCR targeting NS, The authors have no other funding or conflicts of respiratory symptoms and 44% of those NP or VP genes, and it is included in several interest to disclose. 32 Address for correspondence: Ville Peltola, MD, PhD, without symptoms were positive for HBoV1 commercially available multiplex respiratory Department of Pediatrics, Turku University Hos- DNA.11 Furthermore, 70% of the HBoV1 virus PCR panels. Type-specific primers or pital, P.O. Box 52, 20521 Turku, Finland. E-mail: DNA positive children with symptoms were nonspecific primers followed by sequencing [email protected]. positive also for another respiratory virus, of the PCR product can be used for the differ- 2 Copyright © 2013 by Lippincott Williams & Wilkins ISSN: 0891-3668/13/3202-0178 most commonly human rhinovirus. The mere entiation between HBoV types. Quantitative DOI: 10.1097/INF.0b013e31827fef67 presence of HBoV1 DNA in the nasopharynx PCR may be useful for judging the clinical February 178 | www.pidj.com The Pediatric Infectious Disease Journal • Volume 32, Number 2, February 2013 2013 The Pediatric Infectious Disease Journal • Volume 32, Number 2, February 2013 Bocavirus Infections

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