Host factors influencing viral persistence

Allan Randrup Thomsen; A Nansen; Susanne Ørding Andreasen; D Wodarz; Jan Pravsgaard Christensen

doi:10.1098/rstb.2000.0640

Host factors influencing viral persistence

Allan Randrup Thomsen, A Nansen, Susanne Ørding Andreasen, D Wodarz, Jan Pravsgaard Christensen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

24 Citationer (Scopus)

Abstract

Udgivelsesdato: 2000-Aug-29

Originalsprog	Engelsk
Tidsskrift	Philosophical Transactions of the Royal Society of London. Biological Sciences
Vol/bind	355
Udgave nummer	1400
Sider (fra-til)	1031-41
Antal sider	10
ISSN	0962-8436
DOI	https://doi.org/10.1098/rstb.2000.0640
Status	Udgivet - 2000

Bibliografisk note

Keywords: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunologic Memory; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice

Adgang til dokumentet

10.1098/rstb.2000.0640

Citationsformater

@article{395573f0df6711ddb5fc000ea68e967b,

title = "Host factors influencing viral persistence",

abstract = "With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8+ T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.",

author = "Thomsen, {Allan Randrup} and A Nansen and {{\O}rding Andreasen}, Susanne and D Wodarz and Christensen, {Jan Pravsgaard}",

note = "Keywords: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunologic Memory; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice",

year = "2000",

doi = "10.1098/rstb.2000.0640",

language = "English",

volume = "355",

pages = "1031--41",

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T1 - Host factors influencing viral persistence

AU - Thomsen, Allan Randrup

AU - Nansen, A

AU - Ørding Andreasen, Susanne

AU - Wodarz, D

AU - Christensen, Jan Pravsgaard

N1 - Keywords: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunologic Memory; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice

PY - 2000

Y1 - 2000

N2 - With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8+ T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.

AB - With the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. Two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand. Reappearance of virus is associated with impaired long-term CD8+ T-cell mediated immune surveillance, and the time to virus resurgence is inversely correlated to the replication rate of the virus. Our studies also reveal that interferon-gamma is a central cytokine, and depending on the rate of virus replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates that these different outcomes may be explained in relatively simple mathematical terms. This suggests that modelling may be used as a means to predict critical host and virus parameters. Therefore, combining mathematical modelling with precise, quantitative, in vivo analyses looks to be a promising approach in addressing central quantitative issues in immunobiology.

U2 - 10.1098/rstb.2000.0640

DO - 10.1098/rstb.2000.0640

M3 - Journal article

C2 - 11186304

VL - 355

SP - 1031

EP - 1041

JO - Philosophical Transactions of the Royal Society B: Biological Sciences

JF - Philosophical Transactions of the Royal Society B: Biological Sciences

SN - 0962-8436

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ER -