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Original Article
Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains
Firouzeh Farahtaj, Leila Alizadeh, Alireza Gholami, Alireza Tahamtan, Sadegh Shirian, Maryam Fazeli, Amir Sasan Mozaffari Nejad, Ali Gorji, Hamid Mahmoudzadeh Niknam, Amir Ghaemi
Osong Public Health Res Perspect. 2019;10(1):6-11.   Published online February 28, 2019
  • 7,670 View
  • 257 Download
  • 12 Crossref
AbstractAbstract PDF

Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans.


Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus.


Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue.


These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.


Citations to this article as recorded by  
  • Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection
    Prapimpun Wongchitrat, Theerawut Chanmee, Piyarat Govitrapong
    Molecular Neurobiology.2024; 61(5): 2881.     CrossRef
  • Systematic development of immunohistochemistry protocol for large cryosections-specific to non-perfused fetal brain
    Karthika Pandurangan, Jaikishan Jayakumar, Stephen Savoia, Reetuparna Nanda, S. Lata, E. Harish Kumar, Suresh S., Sudha Vasudevan, Chitra Srinivasan, Jayaraj Joseph, Mohanasankar Sivaprakasam, Richa Verma
    Journal of Neuroscience Methods.2024; 405: 110085.     CrossRef
  • Biosensor as an alternative diagnostic method for rabies virus detection: A literature review
    Milad Zandi, Sajad Zandi, Ramin Mohammadi, Parastoo Hosseini, Samane Teymouri, Saber Soltani, Azadeh Rasouli
    Biotechnology and Applied Biochemistry.2022; 69(4): 1348.     CrossRef
  • Immunohistochemical diagnosis of human infectious diseases: a review
    Hamadou Oumarou Hama, Gérard Aboudharam, Rémi Barbieri, Hubert Lepidi, Michel Drancourt
    Diagnostic Pathology.2022;[Epub]     CrossRef
  • Mitochondrial Dysfunction in Rabies Virus-Infected Human and Canine Brains
    Pulleri Kandi Harsha, Sathyanarayanan Ranganayaki, Gowri Yale, Gourav Dey, Kiran K. Mangalaparthi, Anusha Yarlagadda, B. K. Chandrasekhar Sagar, Anita Mahadevan, M. M. Srinivas Bharath, Reeta S. Mani
    Neurochemical Research.2022; 47(6): 1610.     CrossRef
  • A rare fatal case of rabies coexisting with COVID-19
    RabiNarayan Hota, Shalendra Singh, Rakesh Sharma, Pallavi Khandare
    Journal of Acute Disease.2022; 11(3): 129.     CrossRef
  • Enhancement of immune responses by co-stimulation of TLR3 - TLR7 agonists as a potential therapeutics against rabies in mouse model
    Firouzeh Farahtaj, Alireza Gholami, Mohammad Sadeq Khosravy, Safoora Gharibzadeh, Hamid Mahmoudzadeh Niknam, Amir Ghaemi
    Microbial Pathogenesis.2021; 157: 104971.     CrossRef
  • Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
    Thanathom Chailangkarn, Nathiphat Tanwattana, Thanakorn Jaemthaworn, Sira Sriswasdi, Nanchaya Wanasen, Sithichoke Tangphatsornruang, Kantinan Leetanasaksakul, Yuparat Jantraphakorn, Wanapinun Nawae, Penpicha Chankeeree, Porntippa Lekcharoensuk, Boonlert L
    International Journal of Molecular Sciences.2021; 22(21): 11986.     CrossRef
  • Beneficial and Detrimental Effects of Regulatory T Cells in Neurotropic Virus Infections
    Malgorzata Ciurkiewicz, Vanessa Herder, Andreas Beineke
    International Journal of Molecular Sciences.2020; 21(5): 1705.     CrossRef
  • Characterization of the Th17 profile immune response in cases of human rabies transmitted by dogs and its interference in the disease pathogenesis.
    L.B. Santos, F. Guedes, S.M. Achkar, M.I.S. Duarte, I.S.S. Katz, S.R. Silva, E.R. Fernandes
    Journal of Neuroimmunology.2020; 344: 577263.     CrossRef
  • Quantitative proteomics leads to identify dog brain proteins involved in rabies virus infection: implication in understanding viral pathophysiology
    Suchismita Behera, Rajesh Raghunath Pharande, R. Rajendra Reddy, Sharmila B. Majee, Sandeepan Mukherjee, Amol Ratnakar Suryawanshi
    Journal of Proteins and Proteomics.2020; 11(4): 241.     CrossRef
  • Feral dog bite causing paralytic rabies: Difficult diagnosis and failure of prevention
    Hussein Algahtani, Bader Shirah, Emna Chtourou, Osama Abuhawi, Nawal Abdelghaffar, Mohammad Alshehri
    Saudi Journal for Health Sciences.2020; 9(3): 260.     CrossRef
Epidemiologic Features of Animal Bite Cases Occurring in Rabies-Endemic Areas of Korea, 2005 to 2009
Myung Guk Han, Ryou Jung Sang, Young Eui Jeong, Young Ran Ju, Jung Eun Cho, Jun-Sun Park
Osong Public Health Res Perspect. 2012;3(1):14-18.   Published online December 31, 2011
  • 3,067 View
  • 17 Download
  • 3 Crossref
AbstractAbstract PDF
Human rabies is a reemerging infectious disease in Korea. There was no human rabies case for 14 years until the disease had reoccurred in 1999. To prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in Korea was conducted since 2005 as a part of a human rabies control program. The animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (PEP) guideline of the Korea Centers for Disease Control and Prevention.
Information of animal bite cases that occurred from 2005 to 2009 in rabies high-risk regions were collected by cooperation with Regional Public Health Centers in 18 cities/districts of rabies endemic areas.
A total of 2458 animal bite cases were reported. Dogs accounted for 86% of animal bites and 67% of the animals were not vaccinated against rabies virus. For PEP, among rabies-vaccinated animals, 92.7% were observed for clinical signs and 1.4% underwent necropsy. Among unvaccinated animals, 72.7% were observed for clinical signs and 4.1% underwent necropsy. The remaining animals were not available for examination. Of the animal bite patients, 32.5% received PEP and 51.6% were treated by first aid or by washing the wound.
Given that no human rabies cases were reported since 2005 and animal rabies was continuously reported in endemic areas of Korea, the human rabies control program implemented in 2005 appears to have a significant role in the prevention and control of human rabies.


Citations to this article as recorded by  
    Charles E. Rupprecht, Tore Buchanan, Florence Cliquet, Roni King, Thomas Müller,, Boris Yakobson, Dong-Kun Yang
    Journal of Wildlife Diseases.2024;[Epub]     CrossRef
  • Forecasting delay times in post-exposure prophylaxis to human animal bite injuries in Central Iran: A decision tree analysis
    Amir Hamta, Abedin Saghafipour, Seyed Abbas Hosseinalipour, Fatemeh Rezaei
    Veterinary World.2019; 12(7): 965.     CrossRef
  • Characterization of rabies post‐exposure prophylaxis in a region of the eastern Amazon, state of Pará, Brazil, between 2000 and 2014
    N. S. De Paula, E. A. Saraiva, I. M. Araújo, K. K. G. Nascimento, D. A. Xavier, K. S. Santos, E. M. N. Abreu, R. J. P. S. Guimãraes, I. Abel
    Zoonoses and Public Health.2018; 65(4): 395.     CrossRef
Serum MicroRNA Expression Profiling in Mice Infected with Rabies Virus
Myung Guk Han, Jun-Sun Park, Cho Soon Lee, Young Eui Jeong, Jung Sang Ryou, Jung Eun Cho, Young Ran Ju, Kyoung-Ki Lee
Osong Public Health Res Perspect. 2011;2(3):186-191.   Published online December 31, 2011
  • 3,721 View
  • 23 Download
  • 6 Crossref
AbstractAbstract PDF
Serum or plasma microRNAs (miRNAs) are potential biomarkers for the diagnosis for cancer and prenatal diseases. This study was conducted to investigate whether rabies virus causes a change in serum miRNA expression.
ICR mice were intramuscularly inoculated with rabies virus and were sacrificed weekly to collect serum and brain tissue for 4 weeks postinoculation. Mice were assigned to four groups based on the results of indirect immunofluorescent assays, enzyme-linked immunosorbent assay, and nested reverse transcription-polymerase chain reaction and the expression profiles of serum miRNAs were compared using a commercial mouse miRNA expression profiling assay.
The expression levels of miRNAs changed significantly with the different stages of the disease. The expression level of 94 serum miRNAs in infected mice changed at least twofold. Seven microRNAs of them were significantly upregulated or downregulated in all infected mice regardless of disease status. The number of miRNAs with an expression level change decreased with the progression of the disease. In a hierarchical cluster analysis, infected mice clustered into a group separate from uninfected control mice.
Based on the relationship of miRNAs to gene expression regulation, miRNAs may be candidates for the study of viral pathogenesis and could have potential as biomarkers.


Citations to this article as recorded by  
  • Expression Profiling and Bioinformatics Analysis of CircRNA in Mice Brain Infected with Rabies Virus
    Wen Zhao, Jingyin Su, Ningning Wang, Naiyu Zhao, Shuo Su
    International Journal of Molecular Sciences.2021; 22(12): 6537.     CrossRef
  • Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection
    Ryan J. Farr, Christina L. Rootes, Louise C. Rowntree, Thi H. O. Nguyen, Luca Hensen, Lukasz Kedzierski, Allen C. Cheng, Katherine Kedzierska, Gough G. Au, Glenn A. Marsh, Seshadri S. Vasan, Chwan Hong Foo, Christopher Cowled, Cameron R. Stewart, Ron A. M
    PLOS Pathogens.2021; 17(7): e1009759.     CrossRef
  • Machine Learning Identifies Cellular and Exosomal MicroRNA Signatures of Lyssavirus Infection in Human Stem Cell-Derived Neurons
    Ryan J. Farr, Nathan Godde, Christopher Cowled, Vinod Sundaramoorthy, Diane Green, Cameron Stewart, John Bingham, Carmel M. O’Brien, Megan Dearnley
    Frontiers in Cellular and Infection Microbiology.2021;[Epub]     CrossRef
  • MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing
    Leon Tribolet, Emily Kerr, Christopher Cowled, Andrew G. D. Bean, Cameron R. Stewart, Megan Dearnley, Ryan J. Farr
    Frontiers in Microbiology.2020;[Epub]     CrossRef
  • Circulating microRNA profiles of Hendra virus infection in horses
    Christopher Cowled, Chwan-Hong Foo, Celine Deffrasnes, Christina L. Rootes, David T. Williams, Deborah Middleton, Lin-Fa Wang, Andrew G. D. Bean, Cameron R. Stewart
    Scientific Reports.2017;[Epub]     CrossRef
  • Systems Biomedicine of Rabies Delineates the Affected Signaling Pathways
    Sadegh Azimzadeh Jamalkandi, Sayed-Hamidreza Mozhgani, Hamid Gholami Pourbadie, Mehdi Mirzaie, Farshid Noorbakhsh, Behrouz Vaziri, Alireza Gholami, Naser Ansari-Pour, Mohieddin Jafari
    Frontiers in Microbiology.2016;[Epub]     CrossRef

PHRP : Osong Public Health and Research Perspectives