Anti-SAMHD1 Strategies of Feline Immunodeficiency Virus Open Access

Abstract

Human immunodeficiency virus (HIV) is classified as a lentivirus. There are many different lentiviruses that infect various species of primates and non-primates. Feline immunodeficiency virus is a non-primate lentiviruses and it is a more ancestral lentivirus as compared to primate lentiviruses. The goal of this project was to characterize host and virus coevolution for the mechanism that lentiviruses counteract host sterile a motif domain and HD domain-containing protein 1 (SAMHD1) during nondividing myeloid cell infection by employing feline immunodeficiency virus (FIV) and feline SAMHD1 as a model system. SAMHD1 restricts HIV-1 in myeloid cells by depleting cellular dNTPs and suppressing viral reverse transcription. First, I show that FIV does not degrade feline SAMHD1 and SIV viral protein x (Vpx), which proteosomally degrades primate SAMHD1, does not target feline SAMHD1. Next, I showed that human SAMHD1 inhibits FIV infection in human primary monocyte derived macrophages. To show that feline SAMHD1 is a dNTPase in cells, I isolated dNTPs in feline SAMHD1 expressing monocytic THP-1 cells. Indeed, feline SAMHD1 expression lowered dATP and dGTP levels. Then I showed that feline SAMHD1 expression in THP-1 cells inhibits infection of HIV by flow cytometry. Finally, I purified FIV reverse transcriptase (RT). In the future, we will determine the enzymatic efficiency of FIV RT as it compares to HIV-1 RT and simian immunodeficiency virus (SIV) RT. These data demonstrate that, unlike SIV targeting its host SAMHD1 proteosomally by Vpx, FIV does not degrade feline SAMHD1 proteosomally, supporting the possibility that FIV may counteract feline SAMHD1 by its enzymatically efficient RT in myeloid cells as HIV-1 does.

Table of Contents

Introduction………………………………………………………………………………page 1 -4

A.  HIV and AIDS

B.   Virus and host coevolution: an evolutionary arm’s race

C.   Feline Immunodeficiency Virus (FIV)

D.  Cell tropism of lentiviruses: T cells vs. macrophages

E.   SAMHD1 host restriction factor and viral protein x coevolution

F.   HIV-1 RT and SAMHD1

G.  Summary

Results……………………………………………………………………………………..page 5-7

Discussion & Conclusion………………………………………………………………..page 8-9 Figures…………………………………………………………………………………page 10-16

A.  Figure 1……………………………………………………………………………..page 10

B.   Figure 2……………………………………………………………………………..page 11

C.   Figure 3……………………………………………………………………………..page 12

D.  Figure 4………………………………………………………….………………….page 13

E.   Figure 5…………………………………………………………………………….page 14

F.   Figure 6…………………………………………………………………………….page 15

G.  Figure 7…………………………………………………………………………….page 16

Experimental Procedures………………………………………………………………page 17-19

References………………………………………………………………………………page 20-22  

About this Master's Thesis

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Virology
Keyword	FIV, Evolution, Lentivirus
Committee Chair / Thesis Advisor	Kim, Baek, Emory University
Committee Members	Boss, Jeremy, Emory University Hickman, Meleah, Emory University Yu, Daivd Sun-Wen, Emory University Schinazi, Raymond, Emory University

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