Publications by authors named "Sandriana Dos Ramos Silva"

7 Publications

  • Page 1 of 1

Rabies Virus Exposure in Wild Lowland Tapirs (Tapirus terrestris) from Three Brazilian Biomes.

J Wildl Dis 2021 Apr;57(2):443-446

Lowland Tapir Conservation Initiative, Institute for Ecological Research, Campo Grande, Mato Grosso do Sul 79046-150, Brazil.

We evaluated the presence of antibodies for rabies virus in 177 serum samples from 125 wild lowland tapirs (Tapirus terrestris) from three different Brazilian biomes. The rapid fluorescent focus inhibition test was performed. No antibody titers suggesting the circulation of the rabies virus in tapir habitat were detected.
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http://dx.doi.org/10.7589/JWD-D-20-00089DOI Listing
April 2021

Nyctinomops laticaudatus bat-associated Rabies virus causes disease with a shorter clinical period and has lower pathogenic potential than strains isolated from wild canids.

Arch Virol 2019 Oct 10;164(10):2469-2477. Epub 2019 Jul 10.

Pasteur Institute, Av. Paulista 393, São Paulo, SP, CEP 01311-000, Brazil.

Rabies is a lethal viral disease that can affect a wide range of mammals. Currently, Rabies virus (RABV) in some European and American countries is maintained primarily in wild species. The regulation of viral replication is one of the critical mechanisms involved in RABV pathogenesis. However, the relationship between replication and the pathogenesis of RABV isolated from wild animals remains poorly understood. In the present study, we evaluated the pathogenicity of the street viruses Nyctinomops laticaudatus bat-associated RABV (NYBRV) and Cerdocyon thous canid-associated RABV (CECRV). Infection of mice with NYBRV led to 33% mortality with rapid disease evolution and marked histopathological changes in the CNS. In contrast, infection with CECRV led to 67% mortality and caused mild neuropathological lesions. The proportion of RABV antigen was significantly higher in the cytoplasm of neuronal cells of the cerebral cortex and in the meninges of mice infected with CECRV and NYBRV, respectively. Moreover, the replication rate of NYBRV was significantly higher (p < 0.001) than that of CECRV in neuroblastoma cells. However, CECRV replicated to a significantly higher titer in epithelial cells. Our results indicate that NYBRV infection results in rapid disease progression accompanied by frequent and intense histopathological alterations in the CNS in mice, and in a high replication rate in neuroblastoma cells. Although, CECRV is more pathogenic in mice, it caused milder histopathological changes in the CNS and replicated more efficiently in epithelial cells. Our data point to a correlation between clinical aspects of disease and the replication of RABV in different cell lines.
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http://dx.doi.org/10.1007/s00705-019-04335-5DOI Listing
October 2019

Purification of IgG against ribonucleoprotein by a homemade immunoaffinity chromatography column for rabies diagnosis.

J Immunol Methods 2019 08 20;471:1-10. Epub 2019 Mar 20.

Instituto Pasteur, São Paulo, Brazil. Electronic address:

Polyclonal or monoclonal antibodies against rabies virus ribonucleoprotein (RNP) conjugated to fluorescein isothiocyanate (FITC) have been employed for Rabies virus (RABV) antigen detection by the direct fluorescent antibody test (DFA). To date, these biomolecules have been purified by traditional methods such as precipitation by ammonium sulfate or ion exchange chromatography followed by ammonium sulfate precipitation, which allows only for partial detection of the protein of interest. In this study, we aimed to purify anti-RNP polyclonal horse IgG antibodies by cation-exchange chromatography in combination with a homemade immunoaffinity chromatography on RNP immobilized (RNP-IAC). Furthermore, to evaluate the accuracy of the prepared anti-RNP IgG fluorescent antibody in diagnostic purposes, DFA was applied for RABV antigen detection in suspected brain samples of different animal species. The combination of these two techniques made it possible to obtain antibodies with high selectivity and purity. Compared with the performance of the traditional method, anti-RNP IgG antibodies purified by RNP-IAC can be obtained from a smaller volume of hyperimmune serum and with greater avidity. Furthermore, the results obtained by DFA analyses revealed that the prepared anti-RNP IgG fluorescent antibody achieved 100% diagnostic specificity and sensitivity for RABV antigen detection. Thus, two-technique chromatographic, including RNP-IAC technology could be appropriate methods for the purification of polyclonal anti-RNP IgG for the use as a diagnostic reagent for rabies.
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http://dx.doi.org/10.1016/j.jim.2019.03.007DOI Listing
August 2019

Street rabies virus strains associated with insectivorous bats are less pathogenic than strains isolated from other reservoirs.

Antiviral Res 2018 12 26;160:94-100. Epub 2018 Oct 26.

Laboratory of Diagnostic, Pasteur Institute, São Paulo, Brazil. Electronic address:

Rabies is a fatal and viral zoonosis that causes acute, progressive encephalitis and remains an important concern in public health. In the last few years, there has been a change in the epidemiological profile of rabies after implementing canine rabies control in the Americas, which has led to a significant increase in both human and pet cases of rabies associated with insectivorous bats. Thus, it is important to understand the pathogenesis caused by Rabies virus (RABV) isolates from insectivorous bats. Viral growth kinetics, cell-to-cell spread and virus uptake in vitro were analyzed for RABV isolates from Eptesicus furiralis and Myotis nigricans. For pathogenesis evaluation, mice were inoculated with RABV isolates from Eptesicus furiralis and Myotis nigricans, and clinical signs were observed for 40 days. We observed that the insectivorous bat strains showed a higher replication rate, faster cell-to-cell spread and delayed virus uptake in N2a cells. Furthermore, after the first sign of a clinical infection, mice infected with Myotis nigricans and Eptesicus furiralis isolates succumbed rapidly (6 ± 9 days) compared with RABV strains associated with other reservoirs. Our results show that the insectivorous bat RABV strains are less pathogenic for mice than strains associated with other reservoirs. In addition, this study also indicates that the differences in the biological characteristics of the RABV strains are important to their pathogenicity. An enhanced understanding of rabies pathogenesis may be important for the development of novel therapies for humans and in the implementation of rabies control strategies.
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http://dx.doi.org/10.1016/j.antiviral.2018.10.023DOI Listing
December 2018

Infection of neuroblastoma cells by rabies virus is modulated by the virus titer.

Antiviral Res 2018 01 6;149:89-94. Epub 2017 Nov 6.

Laboratory of Diagnostic, Pasteur Institute, São Paulo, Brazil. Electronic address:

Rabies is a lethal viral infection that can affect almost all mammals, including humans. To better understand the replication of Rabies lyssavirus, we investigated if the viral load in brains naturally infected with rabies influences viral internalization and viral growth kinetics in neuroblastoma cells, and if the viral load affects mortality in mice after intradermal infection. We noted that high initial viral loads in brains (group II) were unfavourable for increasing viral titers during serial passages in neuroblastoma cells when compared to low initial viral loads in brains (group I). In addition, group I strains showed higher viral growth and enhanced internalization efficiency in neuroblastoma cells than group II strains. However, we observed that the dominant virus subpopulation in group II promoted efficient viral infection in the central nervous system in the new host, providing a selective advantage to the virus. Our data indicate that rabies infection in animal models depends on not only the virus strain but also the amount of virus. This study may serve as a basis for understanding the biologic proprieties of Rabies lyssavirus strains with respect to the effects on viral replication and the impact on pathogenesis, improving virus yields for use in vaccine development.
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http://dx.doi.org/10.1016/j.antiviral.2017.11.003DOI Listing
January 2018

Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein.

Front Immunol 2017 25;8:1175. Epub 2017 Sep 25.

Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

The heat-labile toxins (LT) produced by enterotoxigenic display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including -generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB) in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV) envelope glycoprotein domain III (EDIII), which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.
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http://dx.doi.org/10.3389/fimmu.2017.01175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622152PMC
September 2017

Immunological aspects of rabies: a literature review.

Arch Virol 2017 Nov 19;162(11):3251-3268. Epub 2017 Jul 19.

Instituto Pasteur, 393, Paulista Avenue, São Paulo, SP, 01311-000, Brazil.

Rabies is a lethal disease caused by the neurotropic virus rabies virus (RABV), and it remains an important public health problem globally. It is known that the host immune response is important for control of viral infection and promoting viral clearance. In this context, it is well documented that, in addition to RABV neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. On the other hand, RABV suppresses host immunity through different mechanisms, for example, direct inhibition of host gene expression, sequestration of pathogen-associated molecular patterns, or modification of cytokine signalling pathways, which hinder the protective host immune responses to RABV infection. Here, we review the immunological aspects of rabies, highlighting innate and adaptive immunity, as well as the host evasion immune mechanisms used by the virus. Finally, we briefly discuss how this knowledge can direct new research and be harnessed for future therapeutic strategies.
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http://dx.doi.org/10.1007/s00705-017-3484-0DOI Listing
November 2017