Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques

Huma Qureshi, Meritxell Genescà, Linda Fritts, Michael B. McChesney, Marjorie Robert-Guroff, Chris J Miller

Research output: Contribution to journalArticle

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Abstract

Ad5 is a common cause of respiratory disease and an occasional cause of gastroenteritis and conjunctivitis, and seroconversion before adolescence is common in humans. To gain some insight into how Ad5 infection affects the immune system of rhesus macaques (RM) 18 RM were infected with a host-range mutant Ad5 (Ad5hr) by 3 mucosal inoculations. There was a delay of 2 to 6 weeks after the first inoculation before plasmacytoid dendritic cell (pDC) frequency and function increased in peripheral blood. Primary Ad5hr infection suppressed IFN-γ mRNA expression, but the second Ad5hr exposure induced a rapid increase in IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC). Primary Ad5hr infection suppressed CCL20, TNF and IL-1 mRNA expression in PBMC, and subsequent virus exposures further dampened expression of these pro-inflammatory cytokines. Primary, but not secondary, Ad5hr inoculation increased the frequency of CXCR3+ CD4+ T cells in blood, while secondary, but not primary, Ad5hr infection transiently increased the frequencies of Ki67+, HLADR+ and CD95+/CCR5+ CD4+ T cells in blood. Ad5hr infection induced polyfunctional CD4 and CD8+ T cells specific for the Ad5 hexon protein in all of the animals. Thus, infection with Ad5hr induced a complex pattern of innate and adaptive immunity in RM that included transient systemic CD4+ T cell activation and suppressed innate immunity on re-exposure to the virus. The complex effects of adenovirus infection on the immune system may help to explain the unexpected results of testing Ad5 vector expressing HIV antigens in Ad5 seropositive people.

Original languageEnglish (US)
Pages (from-to)e106004
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - 2014

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T-cells
Host Specificity
Adenoviridae
Macaca mulatta
Innate Immunity
host range
Blood
T-lymphocytes
Chemical activation
T-Lymphocytes
mutants
Infection
infection
Immune system
Viruses
Messenger RNA
mononuclear leukocytes
immune system
HIV Antigens
Immune System

ASJC Scopus subject areas

  • Medicine(all)

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Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques. / Qureshi, Huma; Genescà, Meritxell; Fritts, Linda; McChesney, Michael B.; Robert-Guroff, Marjorie; Miller, Chris J.

In: PLoS One, Vol. 9, No. 9, 2014, p. e106004.

Research output: Contribution to journalArticle

Qureshi, Huma ; Genescà, Meritxell ; Fritts, Linda ; McChesney, Michael B. ; Robert-Guroff, Marjorie ; Miller, Chris J. / Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques. In: PLoS One. 2014 ; Vol. 9, No. 9. pp. e106004.
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