NEW MICROBIOLOGICA, 36, 211-227, 2013Chikungunya virus infection: an overviewClaudia Caglioti, Eleonora Lalle, Concetta Castilletti, Fabrizio Carletti, Maria Rosaria Capobianchi, Licia Bordi Laboratory of Virology, “L. Spallanzani” National Institute for Infectious Diseases, Rome, ItalyINTRODUCTIONChikungunya virus (CHIKV), an arbovirus trans-mitted by mosquito vectors, is an alphavirus be-longing to the Togaviridae family. Alphavirusesare small spherical enveloped viruses, with a 60-70 nm diameter. The genome is a single-strandRNA molecule of positive polarity, encoding fournon structural (nsP1-4) and three structural pro-teins (C, E1, E2). Viral replication is initiated byattachment of the viral envelope to host cell re-Corresponding authorMaria Rosaria CapobianchiLaboratory of VirologyPadiglione BagliviNational Institute for Infectious Diseases INMI “L. Spallanzani”Via Portuense, 292 - 00149 Rome, ItalyE-mail: [email protected] (Strauss and Strauss, 1994), followed byclathrin-mediated endocytosis of the attached par-ticle (Lee et al., 2013), low pH-mediated membranefusion and delivery of the viral nucleocapsid intothe cytoplasm (Sorisseau et al., 2007). To date noCHIKV interacting protein has been characterized,but in a very recent study, Wintachai et al. identi-fied prohibitin as CHIKV-binding protein ex-pressed by microglial cells (Wintachai et al., 2012).The replication cycle is fast, taking around 4 hours.Alphaviruses are sensitive to dissecation and totemperatures above 58°C (Strauss and Strauss,1994; Khan et al., 2002). About 30 species of arthro-pod-borne viruses are included in the alphavirusgenus, antigenically classified into 7 complexes. These viruses are widely distributed throughoutthe world, with the exception of Antarctica.Besides CHIKV, several arthropod-transmittedalphaviruses cause human disease, characterizedby similar clinical presentation: Barmah ForestChikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, first isolatedin Tanzania in 1952. The main vectors are mosquitoes from the Aedes species. Recently, the establishment of an en-velope mutation increased infectivity for A. albopictus. CHIKV has recently re-emerged causing millions of infectionsin countries around the Indian Ocean characterized by climate conditions favourable to high vector density. Importationof human cases to European regions with high density of suitable arthropod vectors (such as A. albopictus) may trig-ger autochthonous outbreaks. The clinical signs of CHIKV infection include non-specific flu-like symptoms, and a char-acteristic rash accompanied by joint pain that may last for a long time after the resolution of the infection. The deathrate is not particularly high, but excess mortality has been observed in concomitance with large CHIKV outbreaks. De-regulation of innate defense mechanisms, such as cytokine inflammatory response, may participate in the main clin-ical signs of CHIKV infection, and the establishment of persistent (chronic) disease. There is no specific therapy, andprevention is the main countermeasure. Prevention is based on insect control and in avoiding mosquito bites in en-demic countries. Diagnosis is based on the detection of virus by molecular methods or by virus culture on the first daysof infection, and by detection of an immune response in later stages. CHIKV infection must be suspected in patientswith compatible clinical symptoms returning from epidemic/endemic areas. Differential diagnosis should take into ac-count the cross-reactivity with other viruses from the same antigenic complex (i.e. O’nyong-nyong virus).KEY WORDS: CHIKV, Arbovirus, Virus dissemination, Immunopathogenesis, Geographic distribution, Diagnosis,Treatment and prevention.SUMMARYReceived May 26, 2013 Accepted May 30, 2013(BFV) and Ross River viruses (RRV) (Oceania),O’nyong-nyong (ONNV) and Semliki Forest virus-es (SFV) (Africa), Mayaro (South America),Sindbis (SINV) and Sindbis-like viruses (Africa,Asia, Scandinavia and Russia) (Taubiz et al.,2007). Chikungunya fever (CHIKF) derives itsname from Makonde, a language spoken in southTanzania, and means “that which bends up”, re-ferring to the posture of patients afflicted withsevere joint pain characterizing this infection.First isolated in Tanzania in 1952 (Robinson,1955), CHIKV attracted worldwide attentionwhen it caused a massive outbreak in the IndianOcean islands (Enserik, 2006). Since 1952,CHIKV has caused a number of epidemics, bothin Africa and in Southeast Asia, many of them in-volving hundreds of thousands of people. After afew years of relative dormancy in La RéunionIsland, CHIKV transmission has restarted, re-newing concerns about the possibility of renewedautochthonous transmission in Mediterraneancountries.GEOGRAPHIC DISTRIBUTION CHIKF has an epidemiological pattern with bothsporadic and epidemics cases in West Africa,from Senegal to Cameroun, and in many otherAfrican countries (Democratic Republic ofCongo, Nigeria, Angola, Uganda, Guinea, Malawi,Central African Republic, Burundi, and SouthAfrica). Moreover, many epidemics occurred inAsia (Burma, Thailand, Cambodia, Vietnam,India, Sri Lanka, Timor, Indonesia, and thePhilippines) in the 1960s and in the 1990s(Pialoux et al., 2007; Jain et al., 2008). Major epidemics appear and disappear cyclical-ly, usually with an inter-epidemic period rang-ing from 7 to 20 years. The huge outbreak thatincreased concern about CHIKV started inKenya in 2004, where the seroprevalence ratesreached 75% in Lamu island (Pialoux et al.,2007), before reaching the Comores, Seychelles,and Mauritius islands. The virus reached LaRéunion island in March-April 2005, probably212 C. Caglioti, E. Lalle, C. Castilletti, F. Carletti, M.R. Capobianchi, L. BordiFIGURE 1 - Geographic distribution of CHIKV shown in the most recent map (May 2012) retrieved from the CDCwebsite (http://www.cdc.gov/chikungunya/map/index.html, last accessed May 2013).as a result of importation of cases among immi-grants from the Comores and rapidly spread toseveral countries in the Indian Ocean and India(Enserik, 2006; Mavalankar et al., 2007).Compared to earlier outbreaks, this episode wasmassive, occurred in highly medicalized areassuch as La Réunion, and had very significanteconomic and social impact. Since the beginningof the outbreak in the Indian Ocean region, morethan 1,000
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