Latent infection of human bocavirus accompanied by flare of chronic cough, fatigue and episodes of viral replication in an immunocompetent adult patient, Cologne, Germany

Abstract

Introduction:The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far.Case presentation:An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence in situ hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear single-stranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity.Conclusion:On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.

Human Bocavirus Infection of Permanent Cells Differentiated to Air-Liquid Interface Cultures Activates Transcription of Pathways Involved in Tumorigenesis

“…It is mainly associated with respiratory infections in all age groups (subtype 1) (reviewed by [ 5 , 6 ]), but may also display gastrointestinal symptoms (subtypes 2–4) (reviewed by [ 5 ]). After the identification of a covalently closed circular DNA [ 7 ] that most likely represents the form of a persisting genome, we and others have shown that HBoV is able to persist and induce long lasting infections in adults that result in a subclinical asymptomatic course [ 8 , 9 , 10 , 11 ] or that may go ahead with chronic symptoms like cough [ 12 ]. These data were confirmed by several findings from other groups [ 13 , 14 , 15 ] and led to the hypothesis that the virus may take a related pathophysiological route like the human hepatitis B virus by inducing fibrosis, followed by cancerogenesis in its target organs [ 16 ].…”

Human bocavirus 1 respiratory tract reactivations or reinfections in two adults, contributing to neurological deficits and death

“…Encephalitis, myocarditis and hepatitis have also been reported in children infected with HBoV2-3 [2,3]. However, HBoV1 infections in adults are infrequent and documented endogenous or exogenous reinfections are rare [7][8][9][10]. In this study we report two fatal cases of adults with reactivations or reinfections of HBoV1 with respiratory tract illness and neurological deficits.…”

Molecular screening of the human parvoviruses B19 and bocavirus 1 in the study of congenital diseases as applied to symptomatic pregnant women and children

“…HBoV1 is not strictly a respiratory virus; it can produce viraemia and has been detected in the enteric tract, even in healthy adults [ 19 ]. The natural history of the infection has not been clearly elucidated, but it is known that HBoV1 can establish persistent infections [ 20, 21 ] and latent or episomal HBoV1 DNA has been detected in normal and pathological host tissues (tonsils, adenoids, colon) [ 18, 22–24 ]. Reinfections without clinical manifestations are also possible [ 16, 21 ].…”