Table 1.
(a) Acute Stage 1-6 dpi | (b) Convalescent Stage 7-34 dpi | (c) Persistent stage >35 dpi | Reference | ||
---|---|---|---|---|---|
Symptoms | Fever, rash, joint swelling, lymphopenia | Resolution of fever and lymphopenia | Not determined | [42,51,53,59,74] | |
Rash and joint swelling resolving | |||||
Virus Detection | Virus detectable in the blood, lymph nodes, liver, and spleen | Virus detectable in the liver, lymph nodes, spleen, joints, muscles, and organs | Virus detectable in the liver, spleen, joint synovial tissue, and muscle | [42,51,53,59,61,74,75,76,77] | |
Innate Response | Active monocyte and mDC in the blood | Robust pDC, mDC, & monocytes/macrophages | Not determined | [33,34] | |
Cytokine and Chemokine Production | Increased IFN-α/β & γ, IL-6, TNF-α, IL-15, IL-1Ra, IL-2, CCL-2, CCL-3, CCL-4, & VEGF | Increased levels of IFN-γ, TNF-α, IL-2, CCL-2, CCL-3, & CCL-4 | Not determined | [42,53,59] | |
Virus-Specific Immunity | Virus-specific immunity is developing |
T-Cell Response: Virus-specific CD4+ and CD8+ (EM and CM) |
T-Cell Response: Not determined |
[42,51,53,59,61,78] | |
B-Cell Response: Virus-specific IgM & IgG |
B-Cell Response: Virus-specific IgG |
(a) During the acute stage of infection (1–6 dpi) CHIKV infection of NHPs results in viremia lasting an average of 4–5 days, fever, rash, and joint swelling. A reduction in numerous cell populations of the blood results in monocytopenia, lymphopenia, granulocytosis, and thromobocytopenia. The innate immune response is also initiated during the acute stage, supported by evidence of an increase in the number of monocytes and mDCs in the peripheral blood. Effectors of the type 1 IFN response are detected early in the acute stage, along with other proinflammatory cytokines/chemokines. (b) The convalescent stage of infection (7–34 dpi) is marked by dissemination of the virus from the blood to other organs of the body including the liver, lymph nodes, spleen, joints, muscles, and organs. The innate immune response continues, and the adaptive immune response is initiated during this stage of infection, including T and B-cell responses, and the production of both IgM and IgG virus specific antibodies. (c) During the persistent stage of infection (>35 dpi) in NHPs, virus remains detectable in the liver, spleen, joint synovial tissues, and muscle. CHIKV is capable of persisting within NHP CD68+ macrophages of the spleen. Virus specific IgG antibody responses have also been detected during this stage.