Bocavirus: What is it? Pathogenesis, Causes, Symptoms, Diagnosis, Treatment and Long-Term Consequences

HBV has been found in individuals of all ages, although it mainly affects babies 6-24 months with respiratory symptoms.

Human bocavirus ( HBV ) is a parvovirus isolated about a decade ago. It is found worldwide in respiratory samples, primarily in early life and in children 6 to 24 months of age with an acute respiratory infection, and feces samples from patients with gastroenteritis.

Human bocavirus (HBV) is a parvovirus first identified in 2005 using a protocol based on DNase treatment, random PCR amplification, high-throughput sequencing, and bioinformatic analysis.

This virus detection technique was initially applied to nasopharyngeal swabs and washes from children with unresolved respiratory tract infections. It gave a positive result rate of 3.1%; therefore, HBV was proposed to be a pathogen that causes respiratory problems and tract diseases.

Subsequently, three additional subtypes of HBV were identified in human stool samples, termed HBV 2, HBV 3, and HBV 4, to differentiate them from the first isolated subtype, termed HBV 1.

In particular, studies of both respiratory and fecal samples have demonstrated the presence of HBV in association with other potential pathogens, leading to the hypothesis that the virus may be a harmless passenger rather than a true pathogen.

Additionally, the virus has been detected in other biological samples, including blood, saliva, feces, urine, and environmental samples, including river water and sewage. Conversely, recent research has raised concerns about its presence in transfusion medicine.


However, according to Koch’s modified postulates, the virus cannot yet be confirmed as a causative agent of the disease due to the lack of animal models and the difficulties of replicating it in cells cultured in vitro.

Therefore, research and discussion on the potential role of this pathogen (alone or in combination with other types of viruses) in patients with respiratory infections and gastroenteritis are ongoing.


The pathogenesis of HBV remains poorly characterized, mainly due to the lack of specific cell lines for the cultivation of viruses or experimental animal models.

The first study to present an in vitro culture system for HBV dates back to 2009, in which pseudostratified HAE-ALI, derived from primary human bronchial epithelial cells, was used as a tool for HBV replication.

The HAE-ALI model was previously used to infect a wide range of respiratory RNA viruses, such as influenza viruses and human coronaviruses, from the apical surface, as opposed to respiratory DNA viruses, which were achieved only from the basolateral surface.

HBoV1 virions can productively and persistently infect HAE on the apical and basolateral surfaces.

However, a consequence of this infection may be the induction of airway epithelial damage, evidenced by loss of cilia, rupture of the tight junctional barrier, and hypertrophy of epithelial cells.

The virus enters the host through the respiratory tract and the bloodstream or by direct ingestion, reaching the gastrointestinal tract.

HBV 1 has been detected in the respiratory and gastrointestinal tracts. Several studies have shown the association between HBoV1 and the upper and lower respiratory tract.

In this sense, the most frequently described clinical presentation of HBV 1 infection includes:

HBV 1 DNA has also been found in stool samples from adult patients with nausea, vomiting, and diarrhea gastrointestinal manifestations.

However, the HBV 1 load in stool samples from pediatric patients with acute gastroenteritis was lower than the viral load in respiratory tract samples.

A median viral load of 1.88 × 104 genome/ml has been reported for stool samples, which is lower than that found in nasopharyngeal aspirates (NPCs) from patients with respiratory infections (4.9 × 10 3 copies/ml.

HBV 2 and the other genotypes are more frequently found in stool samples, and HBV 2, and possibly HBV 3, is associated with gastroenteritis. HBV 2 has been the only species isolated from APNs from children hospitalized with acute respiratory infections.

More recent data show that HBV can be directly detected in tissues such as the duodenum, paranasal sinus mucosa, and intestinal biopsies.

Epidemiology (causes) of bocavirus infection

HBV has a worldwide distribution; Its transmission and infection occur throughout the year, but it is predominant during the winter and spring months.

The worldwide distribution of HBV involves infections of the respiratory tract and gastrointestinal tract (as evidenced by stool samples) of children and adults in Europe, Asia, the Americas, Africa, and Australia.

The global prevalence of infection was estimated based on a search for articles published in the Medline database from September 6, 2005 (the year of HBV discovery) to March 15, 2016, including studies evaluating respiratory and gastrointestinal infection.

For each country, estimates of prevalence, 95% confidence intervals (CI), and percentage of co-infections were calculated based on pooled data from all eligible studies, and data was extracted into a customized database.

Three hundred fifty-seven reports on the prevalence of HBV correlated with respiratory diseases and gastrointestinal infections.

HBV seroprevalence is age-related and ranges from about 40% in children between 18 and 23 months to nearly 100% in children older than two years, with 76.6% in children and 96% in children. Adults.

In contrast, the observed discrepancy in HBoV2 seroprevalence (70.5% vs. 20.4%) is more likely due to differences in the methods used.

Although the enzyme-linked immunosorbent assay (ELISA) indicates the exposure rate of accumulated infections, the PCR results only reveal an ongoing condition.

Symptoms of bocavirus infection

Common symptoms:

  • Cough: the most common. 25% of cases develop whooping cough as a spasmodic cough.
  • Nasal congestion.
  • Fever.
  • Difficulty breathing.
  • Sickness.
  • Diarrhea.

Less frequent symptoms:

  • Conjunctivitis.
  • Eruption.
  • Maculopapular erythema (small, red, raised flat rashes).

It is often seen on the chest, but a few rashes can also be seen on the face.


The diagnostic tools for identifying the etiologic agents associated with respiratory and gastroenteric diseases have been limited for many years.

The primary method for detecting HBV infections in respiratory and gastrointestinal samples was represented by a direct tool, conventional PCR, followed by nested and real-time (RT) –PCR.

PCR techniques isolate viral genome fragments from NPA, bronchoalveolar, stool, serum, and urine samples by amplifying NP1, NS1, and the VP1 / 2 gene regions or other detection based on the nucleic acid.

Treatment of bocavirus infection

Probiotics help shorten clinical episodes.

So far, there is no specific antiviral therapy recommended against the human mouth virus. However, the studies show a definite beneficial effect of administering probiotics.

Probiotics shorten the duration of episodes and decrease the severity of symptoms by approximately 25-60%.

Therefore, a daily dose of 10 to 10 Lactobacillus Acidophilus colony units (NCFM) is recommended each year from November to April (inclusive). This can also be administered in combination with Bifidobacterium Lactis (B1-07).

Both lactobacilli and bifidobacteria are considered safe for long-term use. However, they should only be administered to healthy children under the supervision of the attending physician.

The incidence of HBV1 infection in children younger than six months is significantly low. Most babies are under six months. Are breastfed. Human breast milk is known to have prebiotic and probiotic properties.

Therefore, this 6-month probiotic regimen may even be of prophylactic value in otherwise healthy children.

Long-term consequences

There is some concern that HBV may be the cause of:

  • Persistent wheezing disorder in children.
  • Asthma: multiple attacks of acute exacerbation.
  • Frequent otitis media.
  • Repeated lower respiratory tract infections.

The reports are compelling, but this discovery is still in its infancy, and more studies are needed to confirm the role of the human mouth virus in chronic airway inflammation.

Conclusion and future challenge

Based on current data, the pathogenic roles of the various HBV genotypes in respiratory tract diseases and gastrointestinal infections remain unresolved.

The virus may be both a passenger and a pathogen causing acute respiratory and gastrointestinal diseases.

The contradictory ideas about this pathogenic role stem mainly from the fact that Koch’s revised postulates cannot be applied to HBV because, to date, there is no practical method for the culture of viruses or an animal model of infection.

Furthermore, several studies have indicated that HBV requires the presence of other agents to carry out infection.

Recent studies have shown that HAE-ALI HBV 1 infection induces a DNA damage response that facilitates amplification of the viral genome.

However, more research is needed to develop suitable cell lines and animal models for viral replication to obtain more evidence to understand the natural course of HBV infection better.

In this regard, more straightforward culture methods and infectious clones should be available, as genomic analysis of HBV is difficult for this reason alone.

Despite a relatively substantial amount of knowledge on the molecular basis of the HBV life cycle, the function of various HBV proteins still requires further investigation.

For example, only recently were three novel NS proteins (NS2, NS3, and NS4) identified; Among these, only one NS protein is critical for virus replication in the epithelium of polarized human bronchial airways.

The role of the other proteins remains quite uncertain.

Most studies have been conducted on the HBV genotype 1, while little information is available on the other agents.

It should be noted that the presence of HBV 2, HBV, and HBV 4 in the respiratory tract should be further investigated and their phylogenetic relationships.

As other authors show, our phylogenetic analysis suggests that HBV 3 may result from the recombination of HBV 1 and HBV 2. Still, it can also be a hybrid of HBoV1, with a common ancestor of HBV 2 and HBV 4.

In this regard, it would be appropriate for future studies to evaluate more and at the same time (possibly all) genotypes and genes.

HBV subtypes have been found worldwide, without regional, geographic, or border restrictions. HBV 1 is associated with pediatric respiratory diseases but also with gastrointestinal symptoms.

HBV 2, HBV 3, and HBV 4 are most frequently detected in stool samples and appear to be enteric. Also, the most typical age for HBV infection is <2 years of age; it has only rarely been found in adults and the elderly.

Clinical studies would help characterize the disease’s pathogenesis and understand immunity in the diverse populations represented by infants, the elderly, or immunocompromised individuals who respond to HBV infection.

There is also a need to optimize commercial diagnostic reagents and methods for HBV identification.

In general, the detection of HBoV is carried out mainly through molecular techniques (i.e., PCR and RT-PCR); rarely is it performed with serological methods (ie, ELISA, EIA, Western blotting, and immunofluorescence) due to the lack of commercial kits.

Furthermore, developing new sequence-independent amplification techniques combined with next-generation sequencing platforms is worthy of achieving rapid and simultaneous detection of numerous pathogens.

Finally, if the pathogenic role of HBV is to be confirmed, developing an effective vaccine to control the spread of the infection should be of primary importance.

To achieve this goal, many studies have been conducted on HBV viral capsid proteins. Previous research studies have confirmed that VLPs can be used as safe and effective vaccines.

Recently, in vitro studies have shown that HBV VP2 VLPs have good immunogenicity, and analyses in mice have shown that they can induce strong humoral and cellular immune responses, indicating their promise as candidate proteins for the HBV vaccine.

The most recent data suggest that creating non-replicating infectious HBV 1 mutants may represent a new approach to HBV vaccine development.

In conclusion, understanding the natural course of HBV infection, implementing experimental systems to analyze the replication cycle in more detail, and developing specific therapies are essential and urgent needs.