التفاصيل البيبلوغرافية
| العنوان: |
Complete Rescue of HTLV-1 p12KO Infectivity by Depletion of Monocytes Together with NK and CD8 + T Cells. |
| المؤلفون: |
Gutowska, Anna, Sarkis, Sarkis, Rahman, Mohammad Arif, Goldfarbmuren, Katherine C., Moles, Ramona, Bissa, Massimiliano, Doster, Melvin, Washington-Parks, Robyn, McKinnon, Katherine, Silva de Castro, Isabela, Schifanella, Luca, Franchini, Genoveffa, Pise-Masison, Cynthia A. |
| المصدر: |
Pathogens; Apr2024, Vol. 13 Issue 4, p292, 23p |
| مصطلحات موضوعية: |
MONOCYTES, KILLER cells, T cells, CD8 antigen, VIRAL DNA, ANTIBODY titer, ANIMAL rescue |
| مستخلص: |
The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1β were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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