Nafees Ahmad
Member of the Graduate Faculty
Professor, Applied BioSciences - GIDP
Professor, BIO5 Institute
Professor, Immunobiology
Primary Department
Department Affiliations
(520) 626-7022
Research Interest
Nafees Ahmad, Ph.D., Professor of ImmunobiologyResearch Interests:1. Molecular mechanisms of HIV-1 vertical transmission2. Molecular mechanisms of HIV-1 pathogenesis in infants and children 3. Molecular mechanisms of HIV-1 infection in immature and mature mononuclear cells4. Identification and characterization of cellular factors involved in HIV-1 replication in immature and mature mononuclear cells5. Biological activity of anti-HIV compoundsThe main focus of my laboratory is understanding the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) mother-to-infant transmission and pathogenesis of pediatric AIDS (HIV-1 infection in children). Areas of investigation include: Molecular and biological characterization of HIV-1 isolates involved in maternal-fetal transmission; Genetic variability of HIV-1 following mother-to-infant transmission; Viral determinants, including viral heterogeneity, functional conservation/divergence of various HIV-1 genes, presence/absence of motifs in HIV-1 genes, replication efficiency, cell tropism, and cytopathic effects associated with HIV-1 maternal-fetal transmission; Viral and host factors associated with HIV-1 evolution, replication, pathogenesis and disease progression in infected infants and children; Molecular mechanisms of HIV-1 infection in immature and mature mononuclear cells; Kinetics of HIV-1 replication in immature hosts (infants) primary lymphocytes and monocytes/macrophages; Mechanisms of HIV-1 infection in immature and mature mononuclear cells, including entry and post-entry events, HIV-1 gene expression and T-cell development, Biological activity of anti-HIV compounds in tissue culture system of T-cell lines, primary lymphocytes and monocytes/macrophages and receptor/coreceptor cell lines, Characterization of cellular factors in immature and mature mononuclear cells that may influence HIV replication differentially.

Publications

Wellensiek, B. P., Ramakrishnan, R., Bashyal, B. P., Eason, Y., Gunatilaka, A. A., & Ahmad, N. (2013). Inhibition of HIV-1 Replication by Secondary Metabolites From Endophytic Fungi of Desert Plants. The open virology journal, 7, 72-80.
BIO5 Collaborators
Nafees Ahmad, Leslie Gunatilaka

Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication.

Ahmad, N. (2016). Features of maternal HIV associated with lack of vertical transmission. The Open Virology Journal.
Ahmad, N. (2017). Characterization of HIV quasispecies in virologically controlled HIV-infected older patients receiving antiretroviral therapy. Journal of Virology.
Ahmad, N. (2017). Recovery of HIV-mediated Immune Aging of T Cells in Virologically Controlled HIV-Infected Aging Patients on Antiretroviral Therapy. Proceedings of National Academy of Sciences.
Bashyal, B. P., Wellensiek, B. P., Ramakrishnan, R., Faeth, S. H., Ahmad, N., & Gunatilaka, A. A. (2014). Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi. Bioorganic & medicinal chemistry, 22(21), 6112-6.
BIO5 Collaborators
Nafees Ahmad, Leslie Gunatilaka

Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics.