Laboratory of Siddappa Byrareddy, PhD

Our laboratory focuses on understanding host-virus dynamics using molecular biology, virology, immunology, systems biology, and genomic tools to develop prevention strategies for HIV/AIDS and other infectious diseases such as SARS-CoV-2 and Zika virus. We use non-human primate models most often for in vivo studies, while also using small animal models. Our long-term goal is to set up well-controlled clinical cohorts in tandem for testing the disease outcomes in relevant animal models as a synergistic platform for preclinical development of vaccines/therapeutics.

Research Interests

Dynamics of host-virus interaction and development of biologically relevant primate models

Our research is focused on the generation of biologically relevant primate models using Transmitter/Founder viruses (T/F) env. We mostly focus on developing a non-human primate model to study HIV associated neurocognitive disorders (HAND) in relevant animal model in the era of cART. Furthermore, predominant route of HIV-1 infection occurs following sexual contact with vaginal transmission accounting for the majority of all newly acquired infections worldwide. Knowledge on how HIV disseminates within the genital mucosa following initial introduction and subsequent gradual spread to the lymphoid compartments as well as CNS is still elusive. We will address these questions systematically using biologically relevant primate models.

To understand the role of Env Glycosylation in mucosal transmission/host virus interaction

Viral env glycosylation is thought to influence preferential transmission by selecting receptors for cellular entry and rendering its susceptibility to neutralizing antibodies. Our laboratory evaluates the role of env glycans using a set of HIV-1 clade C molecular clones predominantly obtained from transmitted/founder (T/F) viruses of a Zambian cohort. The overall goal of this research is to provide improved understanding of virus-host relationships that promote transmission and contribute to the rate of disease progression following infection, which are in turn critical for effective HIV vaccine design.

Functional Cure of HIV

We are developing strategies aimed at limiting inflammation and improving immune responses in the gut as well as other lymphoid tissues. Our ultimate goal is to develop combinatorial therapeutic intervention strategies for antiretroviral therapy treatment.

Mechanistic studies of NeuroAIDS/Drugs of abuse

We are using the SIV/macaque models to evaluate the brain as a viral reservoir in the setting of antiretroviral treatment. Although most reservoir work has concentrated mostly on CD4+ T cells, these are not the primary infected cells in the CNS, where long-lived macrophages and microglia take this role instead. Furthermore, drugs of abuse are frequently co-morbid with HIV-1 infection and further affects the CNS. We are studying the effects of drugs of abuse/immunotherapy on modulating the effectiveness of antiretroviral treatment by monitoring changes in cellular/immunological markers possibly impacting infection and tissue migration both in brain cells as well as in lymphoid cells.

Zika Virus host-virus interactions

The Zika virus (ZIKV) is a newly emerging pathogen that has resulted in a worldwide epidemic. Our laboratory began working on this virus in late 2016 and developed several leads in order to understand the virus pathogenesis and development of therapeutics. We have demonstrated that intersecting polyamine catabolism pathways with polyamine analogues derivatives can inhibit ZIKV replication. As a result, we are currently investigating polyamine analogues as potential treatment to Zika. We also developed a macaque model for Zika infection in order to understand virus immune cell dynamics, glycosylation, and co-infection with other viruses, such as HIV, dengue virus.

Collaborators

• New Iberia Research Center, University of Louisiana, Lafayette

• Richard Cummings, Harvard University
• James Arthos and Claudia Cicala, NIH
• Nebraska Food for Health Center at the University of Nebraska
• Shilpa Buch, Howard Fox, Courtney Fletcher and Howard E. Gendelman, UNMC
• Philipa Santangelo, Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech, Atlanta
• Ranga Uday Kumar, Molecular Biology & Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research
• Mirko Paiardini, Emory University

Funding

1R21 Supplemental award (Chand PI) “Effects of SARS-CoV-2 Proteins on Airway Mucous Response and Associated LncRNAs

Limiting HIV establishment and maintenance by preserving intestinal immunity

MPI: Byrareddy/Paiardini

Source: NIH/NIAID R01AI129745

In this project, we will explore the therapeutic potential of a combined interleukin (IL)-21 and anti-α4β7 Ab intervention to reduce gut damage and immune activation, improve antiviral responses, and limit the size of the reservoir in ART-treated, SIV-infected rhesus macaques.

The combinatorial effects of opiates and the emerging promoter-variant strains of HIV-1 subtype C on HIV neuropathogensis and latency

MPI: Buch S/Byrareddy S/Fox H.

Source: R01DA041751-01

In this proposal, we plan to investigate the involvement of the combinatorial effects of opiates and the emerging promoter-variant strains of HIV-1 subtype C on HIV neuropathogenesis and latency and to test this hypothesis in a primate model.

Host-Directed Therapy to Augment anti-M tuberculosis in Responses in the Setting of HIV Co-infection and to Sterilize the Tuberculoma

PI: Byrareddy S.

Source: Tulane University