Human Bocavirus

Updated October, 2010

Francesca Bonvicini, Monica Musiani, Marialuisa Zerbini

Virology Guided Medline Search

               The Parvoviridae family consists of small DNA viruses with an isometric morphology. The non enveloped viral particle is about 18 to 24 nm in diameter and the linear, single stranded DNA genome is typically about 5 kilobases. The Parvoviridae family includes two subfamilies, the Densovirinae which infects invertebrates and the Parvovirinae which infects vertebrates. Some viruses of the Parvovirinae subfamily have been recovered from human specimens and/or have been associated with clinical manifestations in humans: these viruses belong to the Dependovirus, Erythrovirus and Bocavirus genus.

               The Erythrovirus and Bocavirus genera include human parvovirus B19 and human Bocavirus respectively. These 2 viruses are the most important viruses of human interest associated with defined clinical manifestations. The closest relative of human Bocavirus are the bocaviruses, bovine parvovirus and canine minute virus, which infect cows and dogs respectively.

Williams JV. Déjà Vu All over Again: Koch's Postulates and Virology in the 21st Century. J Infect Dis. 2010 Jun 1;201:1611-4.
 

Epidemiology Guided Medline Search

               Human Bocavirus has been detected worldwide in respiratory, serum, fecal and urine samples obtained from infants mainly of about 2 years of age (2, 4, 9, 13, 15). Human Bocavirus is most often clinically linked to children less than 3 years of age who are hospitalized for lower respiratory infection (5, 4, 12, 14). Variable results have been reported regarding the seasonality of human bocavirus infection: most studies have detected the virus during the winter season while single reports describe increased numbers of viral infections in spring or summer (11). Until recently, only a few studies have analysed the seroprevalence of human bocavirus in healthy individuals.  A ubiquitous IgG response against human Bocavirus has been found in up to 100% of children aged ≥ 2 years (3).

               The prevalence of human Bocavirus DNA in asymptomatic individuals has been rarely evaluated; Lindner et al. (11) did not find human bocavirus DNA in serum samples from healthy blood donors while Garcia-Garcia et al. (6) detected human bocavirus DNA in 5% of respiratory samples obtained from asymptomatic children. In order to determine a more realistic prevalence of human Bocavirus, future prospective studies should include appropriately age-matched children and adults.

               The presence of human Bocavirus DNA in symptomatic children varies considerably, between 2.7–19% and 0.8–9.1% in patients suffering from respiratory and gastroenteric diseases, respectively (11). These variations in viral prevalence may be explained by differences in the study groups and in the assay used.

               No information is currently available on the routes of human Bocavirus transmission. However, since human Bocavirus can be frequently detected in respiratory and fecal samples, a transmission of the virus via aerosols or direct contact has been presumed (3).

Clinical Manifestations Guided Medline Search

               Human Bocavirus infection has been linked to both respiratory symptoms and gastroenteritis. The unusually high number of coinfections detected in clinical specimens makes the association of human Bocavirus with specific diseases complex. The causative role for human Bocavirus in respiratory tract diseases has been investigated by several well-designed clinical studies and is therefore the only clinical manifestation described in this section.

Acute Respiratory Tract Infections: Human Bocavirus DNA has been frequently detected in subjects with “acute respiratory tract infections” in association with a multitude of other viral and/or bacterial respiratory pathogens. The rate of co-infections reaches up to 91% of cases. In children, symptoms and disease manifestations associated with human Bocavirus infection include pneumonia, bronchiolitis, wheezing, respiratory distress, hypoxia, fever, rhinitis, laryngeal croup and, more rarely, conjunctivitis or rashes. In adults, acute human Bocavirus infections leading to acute respiratory tract infections seem to be rare and have been currently detected mainly in immunocompromised subjects to date (3).

Laboratory Diagnosis Guided Medline Search

               The diagnosis of human Bocavirus infection is based on the detection of both the viral genome in clinical specimens (nasopharyngeal swabs, serum, stool, and urine) and the specific immune response against the viral capsid proteins in serum samples. Kits are not yet commercially available but several home-made procedures have been described for the quantitative evaluation of human Bocavirus DNA and for the detection of human Bocavirus -specific antibodies (7, 8, 10). Kantola et al found that respiratory infections in young children due to human Bocavirus elicited a systemic B cell response, comprising both IgM and IgG (8). Elevated serological titers correlated with high viral loads in the nasopharynx and with viremia.  It is anticipated that specific antibody tests for human Bocavirus plus application of quantitative PCR should allow accurate diagnosis of respiratory infection in the future.

Kantola et al.Serodiagnosis of Bocavirus Infection. Clin Infect Dis.2008 Feb 15;46(4):540-6.

Pathogenesis Guided Medline Search

               The current knowledge of human Bocavirus is evolving. The cells supporting human Bocavirus replication and the mechanism by which the virus leads to clinical manifestations is unknown. Human Bocavirus DNA has been detected at high levels in respiratory tract secretions and animal bocaviruses infect respiratory and gut epitheliums. Thus, human Bocavirus infection of the respiratory epithelium in humans can be presumed. Human Bocavirus DNA has also been detected in blood, suggesting the possibility that a range of cells may support human Bocavirus replication in vivo (1). It has been postulated that children with a high titre of human Bocavirus DNA both in the respiratory tract and blood had contracted a primary infection, while the detection of a low titre in the blood may reflect long-term persistence after clinical recovery; a similar scenario is seen for parvovirus B19V. The presence of human Bocavirus DNA in fecal samples might not reflect an active role in the pathogenesis of gastric disease, but rather natural viral shedding during the acute infection (11).

SUSCEPTIBILITY IN VITRO AND IN VIVO Guided Medline Search In Vitro and In Vivo

               No cell culture systems and animal models have been reported for human Bocavirus in vitro and in vivo susceptibility studies.

ANTIVIRAL THERAPY Guided Medline Search  Smart search

               Antiviral agents are not available.

ADJUNCTIVE THERAPY Guided Medline Search

               None.

ENDPOINTS FOR MONITORING THERAPY Guided Medline Search

               None.

VACCINES Guided Medline Search

               No human Bocavirus vaccines are currently being explored.

PREVENTION OR INFECTION CONTROL MEASURES Guided Medline Search

               No specific strategy to prevent human Bocavirus infection has been formulated.

REFERENCES

1. Allander T, Jartti T, Gupta S, Niesters HG, Lehtinen P, Osterback R, Vuorinen T, Waris M, Bjerkner A, Tiveljung-Lindell A, van den Hoogen BG, Hyypiä T, Ruuskanen O. Human bocavirus and acute wheezing in children. Clin Infect Dis 2007;44:904-910. [PubMed] 

2. Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA 2005;102:12891-12896. [PubMed] 

3. Allander T. Human bocavirus. J Clin Virol 2008;41:29-33. [PubMed] 

4. Arden KE, McErlean P, Nissen MD, Sloots TP, Mackay IM. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol 2006;78:1232-1240. [PubMed] 

5. Arnold JC, Singh KK, Spector SA, Sawyer MH. Human bocavirus: prevalence and clinical spectrum at children’s hospital. Clin Infect Dis 2006;43:283-288. [PubMed] 

6. Garcia-Garcia ML, Calvo C, Pozo F, Perez-Brena P, Quevedo S, Bracamonte T. Human bocavirus detection in nasopharyngeal aspirates of children without clinical symptoms of respiratory infection. Pediatr Infect Dis J 2008;27:358–360. [PubMed] 

7. Kahn JS, Kesebir D, Cotmore SF, D’Abramo Jr A, Cosby C,Weibel C, Tattersall P. Seroepidemiology of human bocavirus defined using recombinant virus-like particles. J Infect Dis 2008;198:41-50. [PubMed] 

8. Kantola K, Hedman L, Allander T, Jartti T, Lehtinen P, Ruuskanen O, Hedman K, Soderlund-Venermo M. Serodiagnosis of human bocavirus infection. Clin Infect Dis 2008;46:540–546. [PubMed] 

9. Kesebir D, Vazquez M, Weibel C, Shapiro ED, Ferguson D, Landry ML, Kahn JS. Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus. J Infect Dis 2006;194:1276-1282. [PubMed] 

10. Lin F, Guan W, Cheng F, Yang N, Pintel D, Qiu J. ELISAs using human bocavirus VP2 virus-like particles for detection of antibodies against HBoV. J Virol Methods 2008;149:110–117. [PubMed] 

11. Lindner J, Karalar L, Schimanski S, Pfister H, Struff W, Modrow S. Clinical and epidemiological aspects of human bocavirus infection. J Clin Virol 2008;43:391-395. [PubMed] 

12. Manning A, Russell V, Eastwick K, et al. Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses. J Infect Dis 2006;194:1283-1290. [PubMed] 

13. Neske F, Blessing K, Tollmann F, Schubert J, Rethwilm A, Kreth HW, Weissbrich B. Real-time PCR for diagnosis of human bocavirus infections and phylogenetic analysis. J Clin Microbiol 2007;45:2116-2122. [PubMed] 

14. Qu XW, Duan ZJ, Qi ZY, et al. Human bocavirus-People’s Republic of China. Emerg Infect Dis 2007;13:165-168.[PubMed] 

15. Vicente D, Cilla G, Montes M, Pérez-Yarza EG, Pérez-Trallero E. Human bocavirus, a respiratory and enteric virus. Emerg Infect Dis 2007;13:636-637.[PubMed]