- E. Gelderen van (1)
- H.Q. Liu (1)
- B.G. Meerburg (1)
- R.J.M. Moormann (1)
- G. Nan (1)
- B.P.H. Peeters (4)
- J. Post (1)
- J.M.J. Rebel (2)
- C.B.E.M. Reusken (1)
- H.I.J. Roest (2)
- V. Schirrmacher (3)
- N. Sun (1)
- Y. Wang (1)
- D. Wei (1)
- H. Wilden (1)
- F.G. Zijderveld van (2)
Clinical microbiology of Coxiella burnetii and relevant aspects for the diagnosis and control of the zoonotic disease Q fever
Roest, H.I.J. ; Bossers, A. ; Zijderveld, F.G. van; Rebel, J.M.J. - \ 2013
Veterinary Quarterly 33 (2013)3. - ISSN 0165-2176 - p. 148 - 160.
bulk-tank milk - pregnant goats - dairy-cows - phase-i - molecular characterization - experimental-infection - natural-history - united-states - netherlands - sheep
Coxiella burnetii is the causative agent of the zoonotic disease Q fever. Since its first recognition as a disease in the 1930s, the knowledge about the agent and the disease itself has increased. This review summarizes the current knowledge on C. burnetii and Q fever, its pathogenesis, diagnosis and control. C. burnetii is a bacterium which naturally replicates inside human or animal host cells. The clinical presentation of Q fever varies per host species. C. burnetii infection in animals is mainly asymptomatic except for pregnant ruminants in which abortions and stillbirth can occur. In humans, the disease is also mainly asymptomatic, but clinical presentations include acute and chronic Q fever and the post-Q fever fatigue syndrome. Knowledge of the pathogenesis of Q fever in animals and excretion of C. burnetii in infected animals is crucial in understanding the transmission routes and risks of human infection. Our studies indicated that infected pregnant animals only excrete C. burnetii during and after parturition, independent of abortion, and that C. burnetii phase specific serology can be a useful tool in the early detection of infection. Domestic ruminants are the main reservoir for human Q fever, which has a major public health impact when outbreaks occur. In outbreaks, epidemiological source identification can only be refined by genotypic analysis of the strains involved. To control outbreaks and Q fever in domestic ruminants, vaccination with a phase 1 vaccine is effective. Future challenges are to identify factors for virulence, host susceptibility and protection.
Q fever in pregnant goats: humoral and cellular immune responses
Roest, H.I.J. ; Post, J. ; Gelderen, E. van; Zijderveld, F.G. van; Rebel, J.M.J. - \ 2013
Veterinary Research 44 (2013)1. - ISSN 0928-4249 - 9 p.
coxiella-burnetii infection - phase-i - t-cells - netherlands - outbreak - mice - lipopolysaccharide - progesterone - vaccination - history
Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C. burnetii infections in domestic ruminants even though these species are the major source of Q fever in humans. To investigate the goat’s immune response we inoculated groups of pregnant goats via inhalation with a Dutch outbreak isolate of C. burnetii. All animals were successfully infected. Phase 1 and Phase 2 IgM- and IgG-specific antibodies were measured. Cellular immune responses were investigated by interferon-gamma, enzyme-linked immunosorbent spot test (IFN-¿ Elispot), lymphocyte proliferation test (LPT) and systemic cytokines. After two weeks post inoculation (wpi), a strong anti-C. burnetii Phase 2 IgM and IgG antibody response was observed while the increase in IgM anti-Phase 1 antibodies was less pronounced. IgG anti-Phase 1 antibodies started to rise at 6 wpi. Cellular immune responses were observed after parturition. Our results demonstrated humoral and cellular immune responses to C. burnetii infection in pregnant goats. Cell-mediated immune responses did not differ enough to distinguish between Coxiella-infected and non-infected pregnant animals, whereas a strong-phase specific antibody response is detected after 2 wpi. This humoral immune response may be useful in the early detection of C. burnetii-infected pregnant goats.
Construction of recombinant Newcastle disease virus Italien strain for oncolytic virotherapy of tumors
Wei, D. ; Sun, N. ; Nan, G. ; Wang, Y. ; Liu, H.Q. ; Peeters, B.P.H. ; Chen, Z.N. ; Bian, H. - \ 2012
Human Gene Therapy 23 (2012)7. - ISSN 1043-0342 - p. 700 - 710.
protein cleavage site - hepatitis-c virus - fusion protein - cancer-therapy - vaccine vector - foreign gene - phase-i - pv701 - expression - infection
Newcastle disease virus (NDV) is a naturally oncolytic virus that has been shown to be safe and effective for cancer therapy. Tumor virotherapy using NDV emerged in the 1950s and has advanced more recently by the increased availability of reverse genetics technology. In this study, we constructed a reverse genetics system based on the virulent and oncolytic NDV Italien strain, and generated two recombinant NDVs carrying a gene encoding either enhanced green fluorescent protein or firefly luciferase. We evaluated the replication and antitumor characteristics of these viruses in vitro and in vivo. Our data showed that the insertion of exogenous reporter genes did not affect NDV replication and sensitivity to type I interferon. The recombinant NDVs kept the property of tumor-selective replication both in vitro and in vivo and strongly induced syncytium formation leading to cell death. Moreover, the recombinant NDVs significantly prolonged the survival of tumor-bearing athymic mice (p=0.017) and suppressed the loss of body weight after intratumoral injection. Taken together, our study provides a novel platform to develop recombinant oncolytic viruses based on the NDV Italien strain and shows the efficiency of recombinant NDV Italien for oncolytic virotherapy of tumors.
The role of wild rodents in spread and transmission of Coxiella burnetii needs further elucidation
Meerburg, B.G. ; Reusken, C.B.E.M. - \ 2011
Wildlife Research 38 (2011)7. - ISSN 1035-3712 - p. 617 - 625.
serological cross-reactions - q-fever infection - home-range size - hantavirus infection - rattus-norvegicus - phase-i - uttar-pradesh - risk-factors - epidemiology - reservoir
Rodents are known to cause massive food losses, but are also implicated as reservoirs for a wide variety of zoonotic pathogens. This review discusses the contribution of rodents in the spread and transmission of Coxiella burnetii, the causative agent of Q-fever. We found that rodents have been implicated as reservoirs for Q-fever, but their role in pathogen maintenance, geographic spread and transmission still remains to be clarified. As there are indications for a role of rodents in Q-fever epidemiology, including during the 2007–10 outbreak in the Netherlands, the overall lack of knowledge on the role of rodents warrants studies into their contribution in transmission of C. burnetii from the sylvatic cycle to the domestic cycle, in within-herd transmission, in transmission to surrounding farms and in direct transmission to humans. Although the basic sylvatic and domestic cycles of C. burnetii infection can operate independently, they will overlap in many instances as many areas in the world are occupied by both domestic and wild animals. This area of Q-fever ecology is of interest and research should focus on this aspect of Q-fever epidemiology and, in particular, on the role of rodents therein. More studies are needed that elicit the exact role of rodents in epidemiology of C. burnetii to further optimise disease control.
In vivo efficacy of systemic tumor targeting of a viral RNA vector with oncolytic properties using a bispecific adapter protein
Bian, H.J. ; Wilden, H. ; Fournier, P. ; Peeters, B.P.H. ; Schirrmacher, V. - \ 2006
International Journal of Oncology 29 (2006)6. - ISSN 1019-6439 - p. 1359 - 1369.
newcastle-disease-virus - selective gene-transfer - fusion protein - antitumor vaccination - glioblastoma-multiforme - phase-i - cells - replication - infection - therapy
The aim of the study was: i) to specifically target tumor tissue by Newcastle disease virus (NDV) with oncolytic properties, ii) to improve the delivery system for systemic application of NDV via a bispecific adapter protein and iii) to investigate anti-tumor activity and side-effects. We selected two oncolytic virus strains, one native and the other recombinant, which showed multicyclic replication patterns in tumor cells. In order to reduce normal cell binding, they were modified by preincubation with a recombinant bispecific protein which blocks the viral native cell binding site and introduces a new binding site for a tumor-associated target (in this study, the interleukin-2-receptor, IL-2R). After intravenous transfer to mice, uptake of modified NDV in liver, spleen, kidney and lung was greatly reduced in comparison to unmodified NDV as determined by RRT-PCR of viral M gene copies. In IL-2R+ tumor bearing mice, the same assay revealed a high replication efficiency of the modified virus in the tumor tissue. Tumor therapy experiments showed that the side-effects induced by systemic application were greatly reduced by the adapter protein and that the anti-tumor effects were mostly undiminished. The demonstration of significant systemic anti-tumor activity of this viral vector suggests potential for augmentation by inclusion of one or more therapeutic genes.
Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein
Bian, H. ; Fournier, P. ; Peeters, B.P.H. ; Schirrmacher, V. - \ 2005
International Journal of Oncology 27 (2005)2. - ISSN 1019-6439 - p. 377 - 384.
oncolytic virus - ovarian-cancer - phase-i - cells - replication - virotherapy - strains - vaccine - vector - pv701
Previously we have demonstrated that a recombinant Newcastle disease virus (NDV) carrying the transgene EGFP can be retargeted to IL-2 receptor positive tumor cells by a bispecific fusion protein alphaHN-IL-2 in vitro. The purpose of the present study was to investigate the specificity and efficiency of gene delivery to tumor cells in vivo via this modified RNA virus. Prior ex vivo infection of murine lymphoma cells by the modified virus resulted in selective EGFP expression in IL-2R+ target tumor cells in vivo. Direct fluorescence microscopy and immunohistology showed viral replication in target positive tumor tissue resulting in much more EGFP expression than in target negative tumor tissue, 24 h after intratumoral injection of the alphaHN-IL-2 modified NDV. A quantitative real-time RT-PCR for EGFP mRNA. confirmed the selective gene expression in IL-2R+ tumor cells. Biodistribution studies showed that EGFP transgene delivery was reduced by 35-100% in liver, spleen, kidney, lung and thymus by the modified virus, while 98% of the transgene was delivered to IL-2R+ tumors. In conclusion, the modification of NDV by the bispecific protein does not compromise severely the efficiency of gene delivery into IL-2R-positive tumors, but greatly reduces viral gene expression in IL-2R-negative tumors and in normal tissues
Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein
Bian, H. ; Fournier, P. ; Moormann, R.J.M. ; Peeters, B.P.H. ; Schirrmacher, V. - \ 2005
International Journal of Oncology 26 (2005)2. - ISSN 1019-6439 - p. 431 - 439.
hemagglutinin-neuraminidase protein - disaggregation shear-stress - single-chain antibody - sialic-acid - erythrocyte aggregation - oncolytic virus - rna viruses - phase-i - infection - mechanism
Much interest exists presently in development of vectors for gene therapy of tumors based on RNA viruses because these viruses replicate in the cytoplasm and do not integrate into DNA. The negative stranded paramyxovirus, Newcastle Disease Virus (NDV) from chicken has the additional advantages of preferential replication in tumor cells and of oncolytic and immunostimulatory properties. We here describe the bispecific fusion protein alphaHN-IL-2 which binds to NDV, inhibits its normal cell binding property and introduces a new binding specificity for the interleukin-2 receptor (IL-2R). We demonstrate selective gene transfer to tumor cells expressing IL-2R via the bispecific fusion protein when using recombinant NDV carrying as marker gene the enhanced green fluorescence protein (NDFL-EGFP). Hemadsorption (HA) and neuraminidase activities (NA) of the HN protein of NDV were shown to be blocked by alphaHN-IL-2 simultaneously and the absence of HA-activity of modified NDV was confirmed in vivo. Retargeted virus-binding to IL-2R positive tumor cells was not sufficient for the process of cellular infection. It required in addition membrane fusion via the viral F-protein. By modification of recombinant NDV with a bispecific molecule, our results demonstrate a novel and safe strategy for selective gene transfer to targeted tumor cells