Text S1 Supporting Information and figure legends Figure S1 Identification of PC5-2 binding to NSCLC cells. Representative microscopy images of CL1-5 cells stained with propidium iodide (a-f, red), anti-M13 monoclonal antibody (g-l, green), and merge (m-r). The binding of PC5-2 to CL1-5 cells (a, g, m) was inhibited by 3 mg/ml (b, h, n), 9 mg/ml (c, i, o), and 27 mg/ml (d, j, p) of SP5-2 in a dose-dependent manner. The control phage and PC5-2 did not bind to CL1-5 cells (e, k, q) and NPC-TW01 cells, respectively. Scale bar: 10 mm. Figure S4 Tumor homing ability of PC5-4 phage. SCID mice bearing NSCLC xenografts were injected i.v. with PC5-4, and phage was recovered after perfusion. Recovery of PC5-4 from the tumor was higher than from control organs. Targeting activity of PC5-4 to tumor tissues was inhibited by SP5-2.  IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity BACKGROUND: Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. METHODS AND FINDINGS: Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. CONCLUSIONS: This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease. In the recent years, emerging and re-emerging tropical infectious diseases have been shown to cause high social and economic impact. Vector-borne infectious diseases such as Dengue, West Nile have been resurging largely due to the spread of insecticide resistance, to socio-demographic changes, and to genetic mutations in the pathogens. More recently, chikungungya fever (CHIKF) has now emerged as the next important infection in South-East Asia, the Pacific region and Europe [1] [2] [3] [4] [5] , making it a major threat that requires immediate attention. Recent epidemic resurgence of CHIKF in several African and Asian countries demonstrated that infection can spread alarmingly rapidly [6] [7] [8] [9] from limited early transmission that then developed into an unprecedented and unexpected epidemic, infecting 38% of the population as occurred in Reunion island [6, 8] . The appearance of cases in Europe, the United States and other countries by travelers returning from known outbreak areas underscores the contributory factors of increased human mobility, tourism, global climate change, and increases in insecticide resistance [10] [11] [12] [13] [14] [15] . In this era of globalization, the threat of such disease epidemics should not be underestimated as such public health events could cripple public health systems and economies.