Virology Commons^™

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

Oncolytic Viruses: Cancer Treatment Going Viral, Rhianna N. Bronson

Chancellor’s Honors Program Projects

No abstract provided.

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) …

Understanding The Impact Of Hiv-1 Genetic Diversity On The Function Of Nef And Its Role In Serinc5 Antagonism, Aaron Leslie Johnson

Electronic Thesis and Dissertation Repository

HIV-1 Nef is a key pathogenic protein, allowing HIV-1 to evade the host immune system by downregulating MHC-I and CD4. Furthermore, it was recently discovered that Nef counteracts the host factor SERINC5 to increase HIV-1 infectivity, but the mechanistic details of the Nef:SERINC5 interaction still need to be explored. Throughout this dissertation, I will explore the hypothesis that the genetic diversity that defines HIV-1 has a pronounced effect on the HIV-1 protein Nef, altering its function between and within group M subtypes. To address this hypothesis I investigated how MHC-I and CD4 downregulation differ among all non-recombinant group M subtypes. …

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR …

Ebola Vp40 In Exosomes Can Cause Immune Cell Dysfunction, Michelle Pleet, Allison Mathiesen, Catherine Demarino, Yao Akpamagbo, Robert Barclay, Sergey N. Iordanskiy, +6 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we …

Transcriptomic Analysis Implicates The P53 Signaling Pathway In The Establishment Of Hiv-1 Latency In Central Memory Cd4 T Cells In An In Vitro Model, Cory White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura Martins, Celsa Spina, Alberto Bosque, +4 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the …

P16ink4a Expression And Immunologic Aging In Chronic Hiv Infection, Susan Ribeiro, Jeffrey Milush, Edecio Cunha-Neto, Esper Kallas, Jorge Kalil, Luiz Felipe D. Passero, Peter W. Hunt, Steven Deeks, Douglas F. Nixon, Devi Sengupta

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited …

Antiviral Cd8(+) T Cells Restricted By Human Leukocyte Antigen Class Ii Exist During Natural Hiv Infection And Exhibit Clonal Expansion., Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker

Microbiology, Immunology, and Tropical Medicine Faculty Publications

CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% …

Cellular Minichromosome Maintenance Complex Component 5 (Mcm5) Is Incorporated Into Hiv-1 Virions And Modulates Viral Replication In The Newly Infected Cells., Steven Santos, Yuri Obukhov, Sergei Nekhai, Tatiana Pushkarsky, Beda Brichacek, Michael Bukrinsky, Sergey Iordanskiy

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. …

Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNA-155 (miR-155) has been shown to play significant roles in the immune response, including in the formation of germinal centers (GC) and the development and maturation of T follicular helper (Tfh) cells. There is in vitro evidence to support a critical role for cellular miR-155 and viral miR-155 homologs in the establishment of gammaherpesvirus latency in B cells. We sought to determine the contribution of miR-155 to the establishment and maintenance of latency in vivousing murine gammaherpesvirus (MHV-68) infection. MHV-68-infected mice deficient in miR-155 exhibited decreases in GC B cells and Tfh cells. However, the frequencies of spleen cells …

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated …

Herpes Simplex Virus And Interferon Signaling Induce Novel Autophagic Clusters In Sensory Neurons, Sarah Katzenell, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong infection in the neurons of trigeminal ganglia (TG), cycling between productive infection and latency. Neuronal antiviral responses are driven by type I interferon (IFN) and are crucial to controlling HSV-1 virulence. Autophagy also plays a role in this neuronal antiviral response, but the mechanism remains obscure. In this study, HSV-1 infection of murine TG neurons triggered unusual clusters of autophagosomes, predominantly in neurons lacking detectable HSV-1 antigen. Treatment of neurons with IFN-β induced a similar response, and cluster formation by infection or IFN treatment was dependent upon an intact IFN-signaling pathway. The autophagic …

Cold Atmospheric Plasma Inhibits Hiv-1 Replication In Macrophages By Targeting Both The Virus And The Cells., Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma …

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …

Role Of The Dna Sensor Sting In Protection From Lethal Infection Following Corneal And Intracerebral Challenge With Herpes Simplex Virus 1, Zachary M. Parker, Aisling A. Murphy, David. A. Leib

Dartmouth Scholarship

STING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING(-/-)) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING(-/-) mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal …

Selective Involvement Of The Checkpoint Regulator Vista In Suppression Of B-Cell, But Not T-Cell, Responsiveness By Monocytic Myeloid-Derived Suppressor Cells From Mice Infected With An Immunodeficiency-Causing Retrovirus, Kathy A. Green, Li Wang, Randolph J. Noelle, William R. Green

Dartmouth Scholarship

Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ~50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …

Use Of Irf-3 And/Or Irf-7 Knockout Mice To Study Viral Pathogenesis: Lessons From A Murine Retrovirus-Induced Aids Model, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Interferon regulatory factor (IRF) regulation of the type I interferon response has not been extensively explored in murine retroviral infections. IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant to LP-BM5-induced pathogenesis. However, further analyses strongly suggested that resistance could be attributed to strain 129-specific contamination of the known retrovirus resistance gene Fv1. Therefore, caution should be taken when interpreting phenotypes observed in these knockout mice, as strain 129-derived genetic polymorphisms may explain observed differences.

Inhibition Of The Host Translation Shutoff Response By Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy, Kerstin Radtke, Luc English, Christiane Rondeau, David Leib

Dartmouth Scholarship

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the …

Myeloid-Derived Suppressor Cells In Murine Retrovirus-Induced Aids Inhibit T- And B-Cell Responses In Vitro That Are Used To Define The Immunodeficiency, Kathy A. Green, W. James Cook, William R. Green

Dartmouth Scholarship

Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and …

Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR^−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.

Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy

Jay Reddy Publications

Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA^k dextramers for cardiac myosin heavy chain (Myhc)-α 334–352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334–352 and IA^k dextramer staining. We also detected Myhc-α 334–352 dextramer⁺ cells in the hearts of CVB3-infected mice. The autoreactive …

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor

Dartmouth Scholarship

The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …