Center for Biomedical Science and Policy

Viruses and Host Membranes

GMU Center for Biomedical Science and Policy

Center for Biomedical Science and Policy Twitter/X

Author Information1

Jacob, R.2; Kefale, M.3; Khanna, J.4; Kim, A.J.5; McLaughlin, M.6; Talwar, R.7

(Editor: Li, M.H.8)

1 All authors are listed in alphabetical order.

2 Briar Woods High School, VA; 3 Chantilly High School, VA; 4 McLean High School, VA, 5 Issaquah High School, WA; 6 John R. Lewis High School, VA; 7 Lakeside School, WA

8 George Mason University, VA

Background: Rabies is a zoonotic disease caused by an unsegmented RNA virus of the Lyssavirus genus. It spreads between animals and humans through contact with mucosal membranes, abrasions, or the saliva of an infected animal, most commonly a dog. The rabies virus travels through the body’s signal transmission pathways to reach the central nervous system and brain. Once it has entered the host, it attaches itself to nerve cells and begins to replicate. The virus then spreads throughout the body through neuronal pathways until it reaches the brain. The incubation period varies widely depending on the location of the bite and the severity of the infection. Once the virus reaches the brain, symptoms increase in severity, starting from flu-like symptoms to hydrophobia and delirium. The infected person enters the prodromal phase, during which they experience significant behavioral and physical changes, such as heightened aggression and pupil dilation. Progression to the “excited” or “furious” rabies phase leads to autonomic dysfunction and vicious, erratic behavior. The infected person may die in this phase or progress to the final stage, paralytic rabies, where they will eventually die [1][2][3].

Objective: This project aims to develop a comprehensive understanding of mechanisms for infectivity (attachment and entry) by defining the landscape of rabies virus research through bibliometrics analysis.

Methods: We obtained metadata related to the rabies virus from the PubMed database through the assistance of our GMU faculty advisors. This dataset encompasses keywords extracted from 8,589 articles published between 1993 and 2022. With guidance from our GMU faculty advisors, we utilized an R script to preprocess the data. This preprocessing involved eliminating articles with missing keywords and transforming the data from a long format to a wide format. Subsequently, we categorized the keywords into three distinct cohorts: 1993-2002, 2003-2012, and 2013-2022. Following data preparation, we conducted trend analysis by plotting the occurrences of keywords within these cohorts. We then transformed the data from its long format into an edge list, representing the co-occurrence of keywords within individual articles. This edge list served as the foundation for our network analysis, which aimed to uncover potential research directions within the field of rabies virus studies. For example, if one article featured keywords A and B, while another article featured keywords B and C, the co-occurrence of keywords A and C hinted at potential research avenues. In the final stages of our analysis, we visualized the networks depicting keyword associations. This visualization allowed us to explore and assess promising research directions within the realm of rabies virus research.

Results: First, an article’s keywords serve as indicators of the central and significant topic addressed in the research articles. Our results illustrated that the predominant research emphasis has revolved around antibodies and phylogeny, and this trend is expected to persist due to the absence of a developed vaccine for advanced stages of Rabies. Notably, the first and second cohorts’ top 10 keywords include the term “antigen,” whereas the third cohort omits it. This implies that antigens have ceased to be a prominent area of focus within Rabies research. Second, the analytical results illustrated that the term “proteins” often relates to infectivity, implying their significant influence on virus attachment and cell entry, ultimately resulting in harm. The rabies virus supports this concept by modifying its envelope proteins to adhere to host cell receptors. It is vital to reinforce host cell receptors to prevent harmful proteins from penetrating. Moreover, studies on the impacts of the rabies virus have broadened to encompass various behaviors such as feeding, homing, sexual activity, and cooperation, in addition to aggression. Finally, the network analysis illustrates the most pertinent terms linked to the rabies virus from 1993 to 2023. The lines that connect these words demonstrate that many articles contain various relevant keywords. Words that are not connected could lead to potential research questions. Some words have larger bubbles because they appear more frequently alongside other relevant words in articles. For example, “molecular sequence data” is notable, appearing 511 times in relation to other words, while “leptospirosis” is less frequent, with only 16 occurrences.

Conclusions: Over time, there has been a noticeable increase in both novel research questions and research approaches in rabies virus studies. Notably, proteins are known to play a crucial role in virus attachment and entry. Also, the trends suggest a discernible rise in specialized research areas, particularly in the domain of behavioral studies.

References

  1. Yousaf, M.Z., Qasim, M., Zia, S., Rehman Khan, M.U., Ashfaq, U.A. and Khan, S., 2012. Rabies molecular virology, diagnosis, prevention and treatment. Virology journal9, pp.1-5.
  2. Rabies Exposure in Healthcare Settings. (2021). Centers for Disease Control and Prevention. https://www.cdc.gov/rabies/specific_groups/hcp/exposure.html
  3. How is rabies transmitted? (2019). Centers for Disease Control and Prevention. https://www.cdc.gov/rabies/transmission/index.html