Antibodies from convalescent patients, are highly neutralizing, and can protect mice against CHIKV infection when given both prophylactically and therapeutically . as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of BRL 37344 Na Salt vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. mosquito vectors. In densely populated regions of susceptible humans it is BRL 37344 Na Salt estimated that the infection rate is between 30%C75% [4,5,6]. The 2004C2007, endemic in the Indian Ocean region and India demonstrated the potential of CHIKV to rapidly spread and establish itself in new geographical regions. In December of 2013, CHIKV achieved autochthonous transmission in the Western hemisphere in the Caribbean Islands [7,8] and subsequently became established in Central and South America, Mexico, and the mainland United States (Florida) . According to the Centers for Disease Control and Prevention (CDC), over 1.5 million cases have occurred in the Western hemisphere . Risk of spread could be reduced with increased vector control such as BRL 37344 Na Salt removal of mosquito breeding sites, mosquito repellent, and community awareness. CHIKV has a 12 kb positive-sense single stranded RNA genome consisting of four nonstructural proteins (nsp1-4) and five structural proteins (capsid, E3, E2, 6k, and E1) . CHIKV is an enveloped virus studded with 80 trimers of E1/E2 dimers . While the cellular receptor for the virus is unknown, CHIKV enters cells via clathrin-mediated endocytosis and the capsid containing genomic RNA is released into the cytoplasm . The nonstructural proteins are translated from the genomic RNA and together form the NSP protein complex that includes the viral RNA-dependent RNA polymerase which is necessary for minus and plus strand genomic RNA replication . The NSP complex also synthesizes the subgenomic RNA from minus-strand RNA that codes for the structural polyprotein. During translation of the structural polyprotein, the capsid autocatalytically cleaves itself, exposing an N-terminal ER localization signal [15,16]. The envelope proteins are folded in the endoplasmic reticulum (ER), and they undergo further processing and glycosylation in the ER and Golgi secretory network before being presented on the plasma membrane. The capsid complex assembles around the genomic RNA and interacts with the envelope proteins at the plasma membrane [17,18]. The virions bud and are released for the next round of FASLG infection. The acute stage of CHIKV disease, in humans, is characterized by rash, high fever, headache, and arthralgia. These symptoms can appear within 3C7 days and typically last for two weeks. After a bite from an infected mosquito, the virus replicates locally in the skin and disseminates via the blood to peripheral joints, muscle, tendons, liver, and lymph nodes. Replication in these tissues results in inflammation, synovitis, and tenosynovitis causing intense pain in the joints, tendons, and muscles. The sub-acute phase of CHIKV or convalescent phase is associated with resolution of viremia, fever, and induction of CHIKV-specific T-cell and antibody immune responses. A significant portion of those infected will enter into the chronic phase of CHIKV disease, characterized by recurring polyarthritis, myalgia, and tenosynovitis [19,20], that can last for months to years post infection [19,21,22,23,24,25]. The prevailing hypothesis is that incomplete clearance of CHIKV from specific tissues leads to chronic infection. Persistent CHIKV may replicate at low levels in the joints and muscles, causing long-term arthritic pain and myalgia. Risk factors in developing persistent CHIKV associated rheumatic manifestations are increased age ( 45 years old), preexisting arthritis or joint disease, hypertension, and increased disease severity during the acute phase of disease . Though considered a relatively benign disease, CHIKV can cause serious, even fatal disease in neonates, aged, and immunocompromised populations. Other underlying medical conditions such as diabetes, cardiovascular disease, neurological disorders, and chronic pulmonary diseases are risk factors for developing severe CHIKV disease . Atypical symptoms include encephalitis, seizures, heart failure and arrhythmias, renal failure, skin lesions, and blindness [26,27,28]. There is documented evidence of perinatal mother-to-child transmission resulting in severe disease, including fever, rash, hemorrhagic disease, and seizures from La Reunion, an Indian Ocean Island.