Many unknown species of human DNA viruses have recently (2005-2013) been discovered by using modern molecular and bioinformatic tools. The clinical and pathogenic roles of these viruses are presently known only fragmentarily; however they were found in symptomatic patients, and some have been shown to cause severe infectious illness, or cancer. Some of these emerging DNA viruses are examined in this thesis: Human Bocavirus 1 (HBoV1), Merkel cell polyomavirus (MCV or MCPyV) and Trichodysplasia spinulosa-associated polyomavirus (TSV or TSPyV). Viruses like these are of fundamental importance in the genesis of not only of acute but also of chronic or late-onset illness. The immunobiology and pathogenesis of these new viruses along with the already known DNA virus (parvovirus B19 or B19) can be found by the immunological and molecular methods.
For years it was thought that parvovirus B19, was the sole human-pathogen among its family members. In 2005 a new pathogenic species, HBoV1 (previously denoted HBoV), was discovered by random-PCR from a nasopharyngeal aspirate. The existing data strongly suggest that HBoV1 causes a respiratory illness in young children. The aim of our study was to increase our knowledge on HBoV1-specific Th-cell immunity by examining T-cell proliferation and cytokine responses in asymptomatic adults. HBoV1-specific response was compared to those elicited by B19. B19-specific Th-cell immunity appears to be more divergent (in terms of cytokine response patterns) than the HBoV1-specific one. The present study also suggests that interleukin-13 (IL-13) response induced by HBoV1 may contribute to the airway pathology like asthma or bronchiolitis.
A novel concept of CD4+ T-cells with cytolytic potential (CD4+ CTL) is emerging. Very recently, CD4+ CTL have been implicated in the control of persistent viral infections, e.g., Epistein-Barr virus (EBV), hepatitis C virus (HCV) and HIV-1. While human parvovirus B19 can establish persistence, yet no data exist on the presence of B19-specific CD4+ CTLs. Detection of vigorous B19-specific granzyme B (GrB) and perforin responses in seropositive individuals points to a role of CD4+ CTL also in B19 immunity. Such cells could function within immune regulation and in the triggering of autoimmune phenomena such as Systemic Lupus Erythematosus (SLE) or rheumatoid arthritis (RA).
The newly discovered MCV resides in approximately 80% of Merkel cell carcinomas (MCC). The integration of MCV genome in-to the genome of host cell has been suggested to be the primary reason for this rare and aggressive skin cancer. Here we studied the T-cell immunity against this carcinogenic virus. We found that interferon-γ (IFN-γ) is the dominant cytokine among MCV-seropositive individuals and suggest that IFN-γ plays an important role in surveillance against MCV-induced disease. Our studies also suggested a role for IL-13 and IL-10 in anti-tumor immunity and immune regulation, respectively.
TSV, while exhibiting high seroprevalence in general population, has been detected in trichodysplasia spinulosa (TS) skin lesions, suggesting an etiological role in this disease. In order to characterize Th-cell immunity against TSV, and to permit its comparisons with MCV-specific Th-cell immunity, we studied TSV and MCV-specific proliferation and cytokine responses in healthy volunteers and in one MCC patient. While an association between humoral and cellular responses was detectable with MCV, it was found to be weaker than the humoral and cellular responses detectable with TSV. Despite the significant homology in amino acid sequences of VP1, Th-cell crossreactivity was not evident between these viruses. As CD8+ T-cells specific for MCV LT-Ag oncoprotein clearly provide an important defence mechanism against MCC, the MCV VP1-specific Th-cells may also be important in preventing the oncogenic process, by suppressing MCV replication with antiviral cytokines such as IFN-γ.
Parvoviruses (HBoV1 and B19) and polyomaviruses (MCV and TSV) induce effector CD4+ T-cell responses that are best known for their ability to protect against viral infections. Besides helper functions, CD4+ T-cell contribute to viral control and elimination by CD4-mediated cytotoxic effector functions. Thus, understanding of the CD4+ T-cell immunity is of key importance in the development of vaccines and therapeutic agents against life threatening infectious pathogens.Not availabl
