Overview
Cell intrinsic antiviral immunity
In our lab we work to characterize cell host restriction factors predominantly in the context of HIV and other retroviruses.
Areas of Focus
Human Immunodeficiency Virus
The human immunodeficiency virus type 1 (HIV-1) env gene encodes the envelope protein, which is a complex of two subunits, gp120 (SU) and gp41 (TM) held together by electrostatic interactions. This viral protein is found on the surface of the virions and is responsible for receptor binding and fusion facilitating virus entry in cells. Due to the importance of the HIV-1
Envelope in HIV-1 infectivity, it is targeted by the host antiviral defense. We are focused on studying host genes that target the envelope glycoprotein of HIV-1 as a means of blocking HIV-1 infection. We are interested in:
1. Elucidating how membrane associated RING-CH (MARCH) proteins target the HIV-1 Envelope glycoproteins to block HIV-1 infections.
2. Understanding the role of serine incorporator 5 (SERINC5) during retrovirus infection.
3. Determining novel host-encoded factors that target the HIV-1 envelope glycoprotein.
Murine Retroviruses
Members of the retrovirus family, Murine Leukemia Virus (MLV) and Mouse Mammary Tumor Virus (MMTV) are common pathogens of mice that are used in research to study the interplay between the host and retroviruses and have served as models for HIV and other human retroviruses. Due to the complexity of the antiviral immune response, a full understanding of host-pathogen interactions needs the integration of in vitro and in vivo data, where the role of cellular restriction factors and the innate immune response are examined in mice. Infections in mouse models have provided important and at times surprising insights into the relationship between hosts and pathogens. We aim to:
1. Use knockout mice to determine the role of host genes during retrovirus infection.
2. Elucidate the effect of host genes on vertical transmission of retroviruses.
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently emerged as an important human pathogen that is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has plagued the world with disease hallmarks including breathing difficulty, fever and malaise. SARS-CoV-2 virions have three proteins in the viral envelope: Spike (S), Envelope (E) and Membrane (M). These viral proteins are critical for virus infectivity and are important targets of host responses. In addition, SARS-CoV-2 encodes a number of factors, termed as accessory proteins, that are critical in modulating the host response thereby allowing the virus to replicate in infected hosts. Our group is interested in:
1. Identifying host genes that target E, M and S and the mechanism(s) they employ to exert
their antiviral effect.
2. Determining the role and function of SARS-CoV-2 accessory proteins during infection.
3. Elucidating the conservation of host defense mechanisms upon coronavirus infection.
