No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients

Ivaska, Lotta E.; Christensen, Andreas; Waris, Matti; Puhakka, Tuomo; Vuorinen, Tytti; Allander, Tobias; Söderlund‐Venermo, Maria; Jartti, Tuomas

doi:10.1093/infdis/jiz166

Cited by 7 publications

(14 citation statements)

References 15 publications

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“…Even if HBoV1 has been shown to often persist in tonsils, the mRNA data revealing viral activity, have been inconclusive (17,18). In our study, HBoV1 DNA persisted in pediatric adenotonsillar tissues at high prevalence; however, the diverse and often low viral loads (10 0 to 10 6 copies/10 6 cells) would rule against major productive replication.…”

Section: Discussioncontrasting

confidence: 61%

“…The virus is capable of productively infecting polarized pseudostratified epithelial cells, mimicking the in vivo milieu of the airway epithelium and causing cell hypertrophy and loss of cilia (2,21,22). HBoV1 DNA is very prevalent (up to 56%) in tonsillar tissues of children with tonsillitis or hypertrophy without symptoms of RTI (11)(12)(13)(14)(15)(16)(17)(18). A common treatment for such ailments is removal of adenotonsillar tissue, which has been shown to decrease the prevalence of particularly DNA viruses, like HBoV1 and adenoviruses, in the nasopharynx (19)(20).…”

Section: Discussionmentioning

confidence: 99%

“…HBoV1 DNA has frequently been detected in both palatine and adenoid (nasopharyngeal) tonsils of children with chronic tonsillitis and hypertrophy but without symptoms of RTI (11)(12)(13)(14)(15)(16)(17)(18). Tonsils could thus be a reservoir for virus spread.…”

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confidence: 99%

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Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection

Perdomo

Mattola

et al. 2021

mBio

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Human bocavirus 1 (HBoV1), a nonenveloped single-stranded DNA parvovirus, causes mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children. HBoV1 often persists in nasopharyngeal secretions for months, hampering diagnosis. It has also been shown to persist in pediatric palatine and adenoid tonsils, which suggests that lymphoid organs are reservoirs for virus spread; however, the tissue site and host cells remain unknown. Our aim was to determine, in healthy nonviremic children with preexisting HBoV1 immunity, the adenotonsillar persistence site(s), host cell types, and virus activity. We discovered that HBoV1 DNA persists in lymphoid germinal centers (GCs), but not in the corresponding tonsillar epithelium, and that the cell types harboring the virus are mainly naive, activated, and memory B cells and monocytes. Both viral DNA strands and both sides of the genome were detected, as well as infrequent mRNA. Moreover, we showed, in B-cell and monocyte cultures and ex vivo tonsillar B cells, that the cellular uptake of HBoV1 occurs via the Fc receptor (FcγRII) through antibody-dependent enhancement (ADE). This resulted in viral mRNA transcription, known to occur exclusively from double-stranded DNA in the nucleus, however, with no detectable productive replication. Confocal imaging with fluorescent virus-like particles moreover disclosed endocytosis. To which extent the active HBoV1 GC persistence has a role in chronic inflammation or B-cell maturation disturbances, and whether the virus can be reactivated, will be interesting topics for forthcoming studies. IMPORTANCE Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown. Our study provides new insights into tonsillar HBoV1 persistence. We observed HBoV1 persistence exclusively in germinal centers where immune maturation occurs, and the main host cells were B cells and monocytes. In cultured cell lines and primary tonsillar B cells, we showed the virus uptake to be significantly enhanced by HBoV1-specific antibodies, mediated by the cellular IgG receptor, leading to viral mRNA synthesis, but without detectable productive replication. Possible implications of such active viral persistence could be tonsillar inflammation, disturbances in immune maturation, reactivation, or cell death with release of virus DNA, explaining the long-lasting HBoV1 airway shedding.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection

Perdomo

Mattola

et al. 2021

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“…1,3 The diagnosis of acute bocavirus infection is based on quantitative polymerase chain reaction (PCR), expression of HBoV1 messenger RNA (mRNA), or serology, as the virus DNA may persist for weeks, even months. 1,[3][4][5][6] Interestingly, a few studies have found HBoV1 DNA in tonsil squamous cell carcinoma tumors, inducing speculations of a possible causal association. 7,8 Tonsils in the oropharynx are in contact with inhaled and ingested allergens and pathogens.…”

Section: Introductionmentioning

confidence: 99%

“…HBoV1 is typically found in such specimens from young children suffering with lower respiratory‐tract infections such as bronchiolitis, wheezing, asthma, or pneumonia 1,3 . The diagnosis of acute bocavirus infection is based on quantitative polymerase chain reaction (PCR), expression of HBoV1 messenger RNA (mRNA), or serology, as the virus DNA may persist for weeks, even months 1,3–6 . Interestingly, a few studies have found HBoV1 DNA in tonsil squamous cell carcinoma tumors, inducing speculations of a possible causal association 7,8 …”

Section: Introductionmentioning

confidence: 99%

Persistent human bocavirus 1 infection and tonsillar immune responses

Ivaska

Silvoniemi

Palomares

et al. 2021

Clinical & Translational All

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Background: Persistent human bocavirus 1 (HBoV1) infection is a common finding in patients suffering from chronic tonsillar disease. However, the associations between HBoV1 infection and specific immune reactions are not completely known. We aimed to compare in vivo expression of T-cell cytokines, transcription factors, and type I/III interferons in human tonsils between HBoV1-positive and -negative tonsillectomy patients. Methods: Tonsil tissue samples, nasopharyngeal aspirate (NPA), and serum samples were obtained from 143 immunocompetent adult and child tonsillectomy patients. HBoV1 and 14 other respiratory viruses were detected in NPAs and tonsil tissues by polymerase chain reaction (PCR). Serology and semi-quantitative PCR were used for diagnosing HBoV1 infections. Expression of 14 cytokines and transcription factors (IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2, Tbet) was analyzed by quantitative reverse-transcription (RT)-PCR in tonsil tissues.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Herpesvirus infections in adenoids in patients with chronic adenotonsillar disease

Ivaska¹,

Silvoniemi²,

Mikola³

et al. 2022

Journal of Medical Virology

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Adenoids and tonsils have gained interest as a new in vivo model to study local immune functions and virus reservoirs. Especially herpesviruses are interesting because their prevalence and persistence in local lymphoid tissue are incompletely known. Our aim was to study herpesvirus and common respiratory virus infections in nonacutely ill adenotonsillar surgery patients. Adenoid and/or palatine tonsil tissue and nasopharyngeal aspirate (NPA) samples were collected from elective adenoidectomy (n = 45) and adenotonsillectomy (n = 44) patients (median age: 5, range:1-20). Real-time polymerase chain reaction was used to detect 22 distinct viruses from collected samples. The overall prevalence of herpesviruses was 89% and respiratory viruses 94%. Human herpesviruses 6 (HHV6), 7 (HHV7), and Epstein-Barr virus (EBV) were found, respectively, in adenoids (33%, 26%, 25%), tonsils (45%, 52%, 23%), and NPA (46%, 38%, 25%). Copy numbers of the HHV6 and HHV7 genome were significantly higher in tonsils than in adenoids. Patients with intra-adenoid HHV6 were younger than those without. Detection rates of EBV and HHV7 showed agreement between corresponding sample types. This study shows that adenoid and tonsil tissues commonly harbor human herpes-and respiratory viruses, and it shows the differences in virus findings between sample types.adenoid, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, nasopharyngeal aspirate, palatine tonsil, respiratory viruses | INTRODUCTIONAdenoids and palatine tonsils (in this article tonsils) are secondary lymphoid tissue and serve as a new in vivo model to investigate virus persistence, latent virus infections, and immune functions. [1][2][3] It is well known that respiratory virus infections are commonly prevalent in tonsils, adenoid, or nasopharyngeal aspirate (NPA) of patients undergoing adenotonsillar surgery. 1,4,5 However, different viruses are not equally distributed between adenoids and tonsils. For example, human bocavirus 1 (HBoV1) seems to have tropism in adenoid tissue (25%). 6 In the recently published SPLIT study, human herpesviruses 6 (HHV6), 7 (HHV7), and Epstein-Barr virus (EBV) were the most common herpesviruses found in the tonsil tissue (50%, 70%, 70%). 7 Furthermore, HHV6, HHV7, EBV, and cytomegalovirus (CMV) have

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No Correlation Between Nasopharyngeal Human Bocavirus 1 Genome Load and mRNA Detection or Serology in Adeno-/Tonsillectomy Patients

Cited by 7 publications

References 15 publications

Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection

Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection

Persistent human bocavirus 1 infection and tonsillar immune responses

Herpesvirus infections in adenoids in patients with chronic adenotonsillar disease

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