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The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection.

Alexandra Melton | Lori A Rowe | Toni Penney | Clara Krzykwa | Kelly Goff | Sarah E Scheuermann | Hunter J Melton | Kelsey Williams | Nadia Golden | Kristyn Moore Green | Brandon Smith | Kasi Russell-Lodrigue | Jason P Dufour | Lara A Doyle-Meyers | Faith Schiro | Pyone P Aye | Jeffery D Lifson | Brandon J Beddingfield | Robert V Blair | Rudolf P Bohm | Jay K Kolls | Jay Rappaport | James A Hoxie | Nicholas J Maness
Viruses | 2024

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Pubmed ID: 39066335

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: 75N94020D00007
  • Agency: NCI NIH HHS, United States
    Id: 75N91019D00024
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI138782
  • Agency: NIH HHS, United States
    Id: S10 OD030347
  • Agency: NIDA NIH HHS, United States
    Id: 75N95020D00007
  • Agency: NHLBI NIH HHS, United States
    Id: 75N92020D00007
  • Agency: NCI NIH HHS, United States
    Id: HHSN261201500003I
  • Agency: ORFDO NIH HHS, United States
    Id: 75N99020D00007
  • Agency: NIH HHS, United States
    Id: 75N98020D00007
  • Agency: NIAID NIH HHS, United States
    Id: UC7 AI180314
  • Agency: NIH HHS, United States
    Id: S10 OD026800
  • Agency: NIH HHS, United States
    Id: P51 OD011104
  • Agency: NCI NIH HHS, United States
    Id: HHSN261201500003C

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Tulane University TNPRC Flow Cytometry Core Facility (access service resource)

RRID:SCR_024611

Core provides analytical flow cytometry services and live cell sorting under enhanced Biosafety Level 2 conditions. Instruments available include six analyzers ranging from 4-30 color acquisition and three sorters using 1-,2-,4-way, and plate sorting between 6-18 colors. Provides experimental and panel design consultation. Provides continued education in seminar format and one-on-one sessions with user.

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Tulane University TNPRC Pathogen Detection and Quantification Core Facility (access service resource)

RRID:SCR_024614

Core provides services for maintaining Specific Pathogen Free status in macaque breeding colonies. Services include antibody detection in serum or plasma by Luminex-based assays and /or ELISA for SPF-agents like SIV, SRV, STLV, B virus, SFV. CMV, RRV, SVV, SV40, and LCV, and non-SPF infectious agents like measles, Burkholderia pseudomallei, Tripanosoma cruzi, Mycobacterium tuberculosis, and SARS-CoV-2. Offers services of cytokines quantification, and molecular assays for detection of SRV, CMV, SFV, and RRV.Performs nucleic acid purification from blood and tissue samples as well as qPRC for SIV viral load in plasma, cells, or tissue.

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Tulane University TNPRC High Containment Research Performance Core Facility (access service resource)

RRID:SCR_024612

Provides full or partial support for researchers seeking to perform BSL3 and BSL2/BSL3 Select Agent studies and provides services for bacterial/viral culture and propagation, sample preparation, and processing of blood, BAL, single cell isolation, flow cytometry, and more. Offers project management assistance in study design, budgeting, and IACUC and IBC preparation. Our standard operating procedures have been tested to ensure consistent practices and have undergone rigorous quality assurance processes to ensure reproducibility. Offers assay services for qPCR, O ink Q100, Biorad Bioplex 200, Meso QuickPlex SQ120 Imager and Microscope Axio Observer.

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Tulane University TNPRC Clinical Pathology Core Facility (access service resource)

RRID:SCR_024609

Clinical Pathology Core performs clinical diagnostic testing for all research and colony animals. This includes complete blood counts, routine chemistry panels, and microbial culture workups. The lab is equipped with Sysmex XN1000v veterinary hematology analyzer, Beckman AU480 chemistry analyzer, and Matrix assisted laser desorption ionization time of flight MALDI-TOF instrument for microbe identification. CPC is staff with American Society of Clinical Pathologist certified licensed Medical Technologists.

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Tulane University TNPRC Unit of Collaborative Research Core Facility (access service resource)

RRID:SCR_024610

Core serves as regional and national resource and center of excellence for biomedical research using Nonhuman Primate Models. Unit is staffed by personnel with expertise in veterinary medicine, research study design, budgeting, database management, IACUC issues, sample acquisition, processing, performing laboratory base assays and shipping.

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Tulane National Primate Research Center (disease-related portal)

RRID:SCR_008167

Center focused on understanding human health problems, including infectious diseases that require the use of nonhuman primates to develop diagnostics, therapeutics and preventive strategies. Primary research interests include developing vaccines, treatments and diagnostic tools for infectious diseases such as AIDS, tuberculosis, CMV, COVID-19, Lyme disease, and malaria. TNPRC has both biosafety level 2 and biosafety level 3 laboratories facilities to accommodate various research needs, and is the only National Primate Research Center with Regional Biosafety Laboratory.

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Tulane University TNPRC Confocal Microscopy and Molecular Pathology Core Facility (access service resource)

RRID:SCR_024613

Core provides research support and training with molecular pathology skills, confocal microscopy, image analysis, and multicolor immunohistochemistry and in-situ hybridization techniques for internal and affiliate scientists. Services include assistance with experimental design, antibody selection, molecular probe selection, fixation and staining protocols, operating fluorescent and confocal microscopes, acquiring and storing imaging data, interpretation of results, and generation of publication-quality images. Image analysis services include assistance with capturing images for evaluation and with use of various image analysis software.

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Tulane University TNPRC Anatomic Pathology Core Facility (service resource)

RRID:SCR_024606

Anatomic Pathology Core is responsible for post-mortem examinations, tissue collection and distribution, fixation, processing, slide preparation, routine and special staining, and diagnostic gross and histologic pathology services. Processes and interprets biopsy specimens for both research and diagnostic purposes and provides tissue trimming, paraffin processing, sectioning, and routine and special staining for clinical and research staff and faculty. APC works closely with clinical veterinarians, and through diagnostic pathology on biopsies and necropsies, plays major role in monitoring and maintaining health of animals in breeding colonies.

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Tulane University TNPRC Virus Characterization, Isolation, Production and Sequencing Core Facility (access service resource)

RRID:SCR_024679

Core is divided into virus characterization, isolation, and production part and next generation sequencing part. Virus Characterization, Isolation and Production component provides virus expansion and characterization, viral titer by plaque and TCID50 assays, live virus neutralization and inhibition assays at both BSL-2 and -3 level including SARS-CoV-2. Next Generation Sequencing component provides expertise in next generation sequencing and genomic services including whole genome, epigenetics, targeted amplicons, and 16S metagenomics.

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