Immune activations and viral tissue compartmentalization during progressive HIV-1 infection of humanized mice

Hang Su, Yan Cheng, Sruthi Sravanam, Saumi Mathews, Santhi Gorantla, Larisa Y. Poluektova, Prasanta K. Dash, Howard E. Gendelman

Research output: Contribution to journalArticle

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Abstract

Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are incompletely understood. These are critical events in studies of HIV-1 pathogenesis and in the development of viral reservoirs after antiretroviral therapy. Moreover, factors affecting the permanence of viral-tissue interactions underlie barriers designed to eliminate HIV-1 infection. To this end we investigated the temporal and spatial viral and host factors during HIV-1 seeding of tissue compartments. Two humanized NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ mouse models were employed. In the first, immune deficient mice were reconstituted with human CD34+ cord blood hematopoietic stem cells (HSC) (hu-HSC) and in the second mice were transplanted with adult mature human peripheral lymphocytes (hu-PBL). Both, in measure, reflect relationships between immune activation and viral infection as seen in an infected human host. Following humanization both mice models were infected with HIV-1ADA at 104 50% tissue culture infective doses. Viral nucleic acids and protein and immune cell profiles were assayed in brain, lung, spleen, liver, kidney, lymph nodes, bone marrow, and gut from 3 to 42 days. Peripheral CD4+ T cell loss began at 3 days together with detection of HIV-1 RNA in both mouse models after initiation of HIV-1 infection. HIV-1 was observed in all tested tissues at days 3 and 14 in hu-PBL and HSC mice, respectively. Immune impairment was most prominent in hu-PBL mice. T cell maturation and inflammation factors were linked directly to viral tissue seeding in both mouse models. We conclude that early viral tissue compartmentalization provides a roadmap for investigations into HIV-1 elimination.

Original languageEnglish (US)
Article number340
JournalFrontiers in immunology
Volume10
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

Fingerprint

Virus Activation
HIV Infections
HIV-1
Hematopoietic Stem Cells
Virus Diseases
HIV
T-Lymphocytes
Thromboplastin
Fetal Blood
Nucleic Acids
Spleen
Lymph Nodes
Bone Marrow
Lymphocytes
RNA
Viruses
Inflammation
Kidney
Lung
Liver

Keywords

  • HIV-1 Seeding
  • Host Immune Responses
  • Host Inflammatory Responses
  • Humanized Mice
  • Immune Activation
  • Viral Tissue Compartments

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Immune activations and viral tissue compartmentalization during progressive HIV-1 infection of humanized mice. / Su, Hang; Cheng, Yan; Sravanam, Sruthi; Mathews, Saumi; Gorantla, Santhi; Poluektova, Larisa Y.; Dash, Prasanta K.; Gendelman, Howard E.

In: Frontiers in immunology, Vol. 10, No. FEB, 340, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are incompletely understood. These are critical events in studies of HIV-1 pathogenesis and in the development of viral reservoirs after antiretroviral therapy. Moreover, factors affecting the permanence of viral-tissue interactions underlie barriers designed to eliminate HIV-1 infection. To this end we investigated the temporal and spatial viral and host factors during HIV-1 seeding of tissue compartments. Two humanized NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ mouse models were employed. In the first, immune deficient mice were reconstituted with human CD34+ cord blood hematopoietic stem cells (HSC) (hu-HSC) and in the second mice were transplanted with adult mature human peripheral lymphocytes (hu-PBL). Both, in measure, reflect relationships between immune activation and viral infection as seen in an infected human host. Following humanization both mice models were infected with HIV-1ADA at 104 50{\%} tissue culture infective doses. Viral nucleic acids and protein and immune cell profiles were assayed in brain, lung, spleen, liver, kidney, lymph nodes, bone marrow, and gut from 3 to 42 days. Peripheral CD4+ T cell loss began at 3 days together with detection of HIV-1 RNA in both mouse models after initiation of HIV-1 infection. HIV-1 was observed in all tested tissues at days 3 and 14 in hu-PBL and HSC mice, respectively. Immune impairment was most prominent in hu-PBL mice. T cell maturation and inflammation factors were linked directly to viral tissue seeding in both mouse models. We conclude that early viral tissue compartmentalization provides a roadmap for investigations into HIV-1 elimination.",
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