Background
Human bocavirus (HBoV) was first described in 2005 by a group of Swedish scientists who identified a previously uncharacterized virus in the respiratory secretions of acutely ill children. [1]
Human bocavirus is a small, single-molecule, linear DNA, nonenveloped virus with a nucleocapsid measuring 18-26 nm and a genome length of 4000-6000 nucleotides. [1, 2] Phylogenetic analysis of the complete genome of human bocavirus (see image below) has shown that the virus is most closely related to the significant veterinary pathogens bovine parvovirus and canine minute virus (hence the name, boca virus), which are members of the genus Bocavirus, family Parvoviridae. A better known member of this family is parvovirus B19.
The genome of human bocavirus. The 4 genes are labeled based on their presumed function, according to homologous genes in other parvoviruses. Nonstructural protein 1 (NS1) is a DNA-binding protein involved in gene transcription. NP1 is also nonstructural and is a highly conserved protein of unknown function. The capsid proteins are viral protein 1 (VP1) and viral protein 2 (VP2).
Nucleic acid amplification via polymerase chain reaction (PCR) has been used to detect human bocavirus in respiratory samples from children with acute respiratory tract infection worldwide. [3, 4] More recently, human bocavirus has been implicated in respiratory tract infections in adults and in acute gastroenteritis in children and adults. However, the pathogenetic role of human bocavirus remains uncertain, as other viruses have often been co-detected in pediatric lower respiratory tract infections positive for bocavirus, [5] and modified Koch's postulates have not yet been fulfilled for this virus. Furthermore, its causative role in respiratory tract infection in adults remains to be elucidated.
Pathophysiology
The pathophysiology of human bocavirus infection is not yet fully understood. Most studies have been retrospective PCR-based analyses of specimens from patients with acute respiratory tract infection. The vast majority of human bocavirus-positive samples have been derived from infants and young children. Viral genome has also been detected in blood and feces, [6] the significance of which remains to be elucidated.
Human bocavirus is often found in the presence of another pathogen or other pathogens in respiratory specimens (33%) and stool samples (56%), [7] raising concerns about its primary role as a causative agent. [8] To further cloud the picture, human bocavirus 2 (HBoV2) and human bocavirus 3 (HBoV3) are newly discovered bocaviruses. [9, 10] In one study, the prevalence of HBoV3 was low, and it was not associated with acute gastroenteritis, while HBoV2 was found to be the third most common cause of pediatric acute gastroenteritis. [11] More recent studies have called into question the role of bocavirus in acute gastroenteritis, however. [12]
HBoV1 virus infection has a clinical presentation that is very similar to that of rhinovirus infection. No association between HBoV and asthma development has been proven, but HBoV does have an association with Th1/Th2 responses in the nasopharyngeal mucosa. [13] Nonetheless, HBoV has been isolated from patient’s respiratory secretions during asthma attacks. Lu et al reported that an additional virus or viruses were detected in up to 77% of cases. Coronavirus and parainfluenza virus were the most common coinfectors (30% and 28%, respectively). Only 22% of patients had an infection with HBoV1 alone. [14]
HBoV type 4 has now been fully sequenced. The gene sequences of strains, 1, 2, 3 and 4 vary considerably, up to 68%-80%. All the bocaviruses have been shown to have the same putative intermediate structures. It is believed that the bocavirus family can be associated with cancer development and respiratory and gastrointestinal diseases.
Bocavirus is considered to be part of the parvovirus family, but their replication is completely different. [15] This virus enters the host through the respiratory system, moves to the bloodstream, and then reaches the gastrointestinal tract. It can also be acquired by oral ingestion. Basaranoglu et al reported two cases of hemophagocytic lymphohistiocytosis (HLH) in which HBoV was detected via PCR of nasopharyngeal secretions. HLH triggered by viral infection does not respond to antiviral therapy. IVIG or steroids may be helpful. [16] HBoV1 infection initiates a DNA damage response (DDR), activating all three phosphatidylinositol 3-kinaserelated kinases (PI3KKs): ATM, ATR, and DNA-PKcs. HBoV1 replicates only in terminally differentiated, non-dividing cells. [17]
Epidemiology
Frequency
HBoV has been found in 10% of respiratory secretions from healthy children during winter months worldwide. In hospitalized patients with respiratory infections, HBoV is detected in up to 18% of cases. [16]
United States
A study by Chow et al (2008) reported that human bocavirus was detected by PCR in respiratory specimens from 4 of 273 (1.5%) hospitalized adults in whom no alternate viral etiology was identified. All had underlying pulmonary disease, and two had underlying cardiac disease. In comparison, respiratory specimens from 36 of 1539 (2.3%) pediatric patients were positive for bocavirus. [18]
International
In 3 studies, human bocavirus was detected via PCR in respiratory secretions from 1 of 126 (0.8%), [19] 3 of 202 (1.5%), [20] , and 3.1% [21] of adults with respiratory tract infection. Five adults hospitalized with bocavirus-associated pneumonia were included in a case series. [22] Another series included one hospitalized and 4 outpatient cases of bocavirus-associated pneumonia in adults. [23]
A 5-year study of immunosuppressed and nonimmunosuppressed children in Mexico yielded the first report of co-infection with human bocavirus and adenovirus. [24]
Serologic responses to human bocavirus infection have also been documented. A 2008 study by Lindner found an immunoglobulin G (IgG) response in 280 of 299 (94%) of adults, while immunoglobulin M (IgM) results were positive in 2 of 299 cases (1%). [25]
Tozer et al (2009) reported positive PCR results using fecal specimens from 18 of 275 (4.8%) adults with acute gastroenteritis. [6]
No seasonal pattern of infection has yet emerged. [23, 26]
Mortality/Morbidity
Human bocavirus has largely been described in young children with acute respiratory tract infection. However, the prevalence and pathogenicity of bocavirus infection in immunocompromised patients is largely unknown. A case of atypical bocavirus-associated pneumonia in an immunocompromised adult has been described. [27]
It is well known that some viruses can cause cancer; some studies have reported an association between HBoV and colon cancer. HBoV was isolated in approximately 25% of patients with colon cancer. Direct causation has not been established; no evidence suggests that infection with HBoV can alter or predict the outcome or degree of colonic malignancy. However, it cannot be disregarded that this virus, specifically genotype 1, has been found in patients with adenocarcinomas, and further studies are needed. [28]
Like many other upper respiratory viral infections, bocavirus infection is self-limited, but some reports have described complications, including fatal ones. Dr. Ursic reported an 18-month-old infant with chronic lung disease of prematurity in whom HBoV1 was the only virus detected. [29] Piñata et al found that HBoV often presents as a co-infector with coronaviruses. The clinical presentation was found to be related to the viral load and the interaction between the HBoV with the host and comorbidities. [30]
Race
Bocavirus infection has no known racial predilection.
Sex
Bocavirus infection has no known sexual predilection.
Age
Human bocavirus has largely been detected in children with respiratory tract infection. One study from Brazil revealed human bocavirus infection in children younger than 2 months, suggesting that the infection may occur at a very early age. [31]
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The genome of human bocavirus. The 4 genes are labeled based on their presumed function, according to homologous genes in other parvoviruses. Nonstructural protein 1 (NS1) is a DNA-binding protein involved in gene transcription. NP1 is also nonstructural and is a highly conserved protein of unknown function. The capsid proteins are viral protein 1 (VP1) and viral protein 2 (VP2).
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Illustration of an electron micrograph of canine parvovirus, which is closely related to human bocavirus.
