Virology Commons^™

Utilizing Fiv (Feline Immunodeficiency Virus) To Develop A Novel Animal Model To Study Hiv (Human Immunodeficiency Virus), Ankita Suryakant Kambli

Electronic Thesis and Dissertation Repository

This project sought to perform the in vitro work needed to accomplish the long-term vision of harnessing the similarities between HIV (Human Immunodeficiency Virus) and FIV (Feline Immunodeficiency Virus) to develop an animal model whereby cats can be used to study HIV pathogenesis and therapeutics. We transfected CRFK (Crandell Rees Feline Kidney) fibroblasts with plasmids that could express human or feline CD4, CCR5, or both, and determined receptor surface expression through flow cytometry. We discovered that HIV envelope expressed on 293T can fuse with huCD4/huCCR5 on CRFK. These cat cell lines were also capable of supporting HIV infection. Additionally, we …

Determining The Relative Transmission Fitness Of Hiv-1 Subtypes A, B, C, And D, Spencer Yeung

Electronic Thesis and Dissertation Repository

There is in vivo evidence that suggests the genetic diversity of HIV-1 subtypes influence heterosexual transmission efficiency. To recapitulate sexual transmission in vitro, blocks of genital tissue were exposed to mixtures of genetically different subtype viruses. Migrating immune cells were collected and co-cultured with a CD4+ T-cell line permissive to HIV infection (PM1) to measure dendritic cell virus transfer; HIV-exposed tissues were cultured separately. Next generation sequencing (NGS) of HIV-1 DNA was used to quantify relative infection rates of the various challenge viruses, and to assess fitness differences in infection of the tissue vs. migratory/T cell co-cultures. Our results …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Hiv-1 Group M Subtype Fitness, Disease Progression, And Entry Efficiency, Colin M. Venner

Electronic Thesis and Dissertation Repository

Human immunodeficiency virus type 1 (HIV-1) emerged in the human population shortly after the turn of the 19th century. Distribution of HIV-1 across the globe over the past 30–35 years can be traced to founder events with primordial HIV strains from sub-Saharan Africa. Even considering the burden of HIV in Africa, our knowledge of HIV-1 disease is still largely limited to subtype B HIV-1, a strain responsible for 3 million infections in North America and Europe as compared to the 33 million that are infected with HIV-1 subtypes A, C, D, and circulating and unique recombinant forms.

This dissertation analyzes …