Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

Abstract

Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-α were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.

Viperin restricts chikungunya virus replication and pathology

“…Total PBMCs were isolated; CD14 + monocytes, CD19 + B cells, CD3 + T cells, and CD56 + NK cells were sorted by flow cytometry (Supplemental Figure 3, A and B); and their transcriptional profiles were analyzed. Consistent with our earlier findings (22), CD14 + monocytes were the major subsets targeted by CHIKV, followed by CD19 + B cells (Supplemental Figure 3C and Figure 2A). Control HI CHIKV did not infect and replicate in any subsets (Supplemental Figure 3C).…”

“…However, despite the induction of an active type I IFN response in patients during the acute phase of the disease (18,19), the mechanisms involved remain unknown. Although recent studies have shed light on the interplay between type I IFNs and CHIKV during infection (20)(21)(22)(23)(24), how CHIKV replication is controlled by ISGs induced by type I IFNs remains to be elucidated (25,26). RSAD2 (encoding virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible [viperin]; also known as cig5) was first reported as an antiviral gene induced by human cytomegalovirus and IFNs (27).…”

Detection of Persistent Chikungunya Virus RNA but not Infectious Virus in Experimental Vertical Transmission in Aedes aegypti from Malaysia

“…Full-length infectious cDNA clones were constructed as previously described 11 for the two CHIKV strains used: ICRES1 (based on LR2006_OPY1, a virus of Indian Ocean sublineage, isolated in Reunion Island; GenBank accession number: DQ443544) and SGP011 (based on SGEHICHD13508, a virus of the Indian sublineage isolated in Singapore; FJ445511), 12 which is closely related to Malaysian viruses ( Figure 1). …”

Recent progress on chikungunya virus research

“…Acute CHIKV infection elicits strong innate immune responses involving the elevation of type I IFN, especially IFN-α, and the production of numerous pro-inflammatory cytokines, chemokines, and growth factors. Studies show that high level of IFN-α is associated with the rapid control of the viremia (Her et al, 2010;Wauquier et al, 2011).…”