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The function of C-type lectins in chikungunya virus attachment and binding

Shackleford, Marcus Shackleford (2023) The function of C-type lectins in chikungunya virus attachment and binding. Master's Thesis, University of Pittsburgh. (Unpublished)

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Chikungunya virus (CHIKV), a mosquito-borne human pathogen, is a global health concern due to natural transmission occurring on five continents with over 10 million recent infections worldwide. CHIKV displays broad cell and tissue tropism, and glycosaminoglycans (GAGs) and MXRA8 have been identified as host molecules that mediate attachment and entry, respectively. However, the characterization of additional host factors that mediate binding and entry into target cells is needed to fully understand the tropism and pathogenesis of CHIKV. Results from an RNA screen targeting host genes in human osteosarcoma (U-2 OS) cells suggest that the C-type lectin receptors (CLRs) DCIR, DC-SIGN, and L-SIGN may function as attachment or entry factors for CHIKV. CLRs are a family of pattern recognition receptors (PRR) that can bind to carbohydrates found specifically on pathogens and function in immune responses to infection. As CHIKV oscillates between vertebrate hosts and mosquito vectors, the type of N-linked glycans on viral glycoproteins differs depending on the host species, which may affect binding to different CLRs, cellular tropism, and immune responses. To determine whether the expression of CLRs facilitates CHIKV binding and infectivity, assays were conducted using stably-transfected Chinese hamster ovary (CHO) WT K1 and GAG-knockout pgsA745 cells that express DCIR, DC-SIGN, and L-SIGN using both mammalian- and mosquito-derived CHIKV. Overall, this work provides a foundational understanding of the interactions of CHIKV with vector and host CLRs. These studies will further our understanding of the interactions between CHIKV and CLRs in the context of binding and infectivity of target cells.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Shackleford, Marcus Shacklefordmas992@pitt.edumas992
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairJenkins, FrankFJENKINS@pitt.eduFJENKINS
Thesis AdvisorSilva, LaurieLAS324@pitt.eduLAS324
Committee MemberMcmilen, CynthiaCMM287@pitt.eduCMM287
Committee MemberTufts, DanielleDMT80@pitt.eduDMT80
Date: 15 May 2023
Date Type: Publication
Defense Date: 4 April 2023
Approval Date: 15 May 2023
Submission Date: 27 April 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 65
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Chikungunya virus, C-type lectin receptors, DC-SIGN, L-SIGN, DCIR, vector borne diseases, zoonotic diseases, viral entry, arbovirus
Date Deposited: 15 May 2023 22:44
Last Modified: 15 May 2023 22:44


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