Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations.

BACKGROUND: Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10-20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components. METHODOLOGY: Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components. Two peptides (A&B) were identified using several bioinformatic tools, synthesised and used to validate the results obtained in silico. An ELISA was designed to assess the immunoreactivity of serum samples from CHIKV patients to these peptides. Further, experiments were conducted in a C57BL/6J experimental mouse model to investigate if peptide A and peptide B were indeed capable of inducing pathology. FINDINGS: The serum samples showed reactivity of varying degrees, indicating that these peptides are indeed being recognized by the host immune system during CHIKV infection. Further, these peptides when injected into C57BL/6J mice were able to induce significant inflammation in the muscles of C57BL/6J mice, similar to that observed in animals that were injected with CHIKV alone. Additionally, animals that were primed initially with CHIKV followed by a subsequent injection of the CHIKV peptides exhibited enhanced inflammatory pathology in the skeletal muscles as compared to animals that were injected with peptides or virus alone. Collectively these observations validate the hypothesis that molecular mimicry between CHIKV E1 protein and host proteins does contribute to pathology in CHIKV infection.

Neuropathological correlate of the "concentric target sign" in MRI of HIV-associated cerebral toxoplasmosis.

Cerebral toxoplasmosis is a frequent cause of focal brain lesions in the setting of immunodeficiency states, particularly acquired immune deficiency syndrome (AIDS), and magnetic resonance imaging (MRI) is an important diagnostic modality to differentiate toxoplasmosis from tuberculoma, and primary central nervous system lymphoma with diverse therapeutic implications. Several imaging patterns have been described in cerebral toxoplasmosis. The "concentric target sign" is a recently described MRI sign on T2-weighted imaging of cerebral toxoplasmosis that has concentric alternating zones of hypo- and hyperintensities. It is believed to be more specific than the well-known "eccentric target sign" in the diagnosis of cerebral toxoplasmosis and hence more useful in differentiation from other focal brain lesions in the context of AIDS. The concentric target sign, seen in deep parenchymal lesions, is distinct from the surface-based cortical "eccentric" target sign. The histopathological correlate of the latter has been recently described, but that of the concentric target sign is not known. In this study we describe the neuropathological correlate of this concentric target sign from the postmortem of a 40-year-old man with AIDS-associated cerebral toxoplasmosis. The concentric alternating zones of hypo/hyper/iso/intensities corresponded to zones of hemorrhage/fibrin-rich necrosis with edema/coagulative compact necrosis/inflammation with foamy histiocytes admixed with hemorrhage forming the outermost zone, respectively. The exclusive specificity of this sign in cerebral toxoplasmosis remains to be further elucidated.

Cysticercal chronic basal arachnoiditis with infarcts, mimicking tuberculous pathology in endemic areas.

Neurocysticercosis (NCC) is the most common of the parasitic diseases affecting the CNS, with protean clinical manifestations. Stroke as a complication of NCC occurs in a very small percentage of cases, mostly involving small perforating vessels while major intracranial vessel involvement is extremely rare. The present report involves two autopsied cases of chronic cysticercal basal arachnoiditis causing large arterial territory infarcts and, in the second case, a hypothalamic mass. They were diagnosed and managed, clinically and by neuroimaging, as stroke and neurotuberculosis, respectively. The diagnosis was established only at autopsy, which revealed NCC causing basal arachnoiditis, major vessel vasculitis and infarcts. Histologically, case 1 showed degenerating racemose cysticercal cyst within the thick basal exudate. In the second case, remnants of the degenerated cysticercal cyst in the form of hooklets and calcareous corpuscles were identified within the giant cell inciting a granulomatous response to form a hypothalamic mass lesion mimicking tuberculoma. The present case report highlights the importance of considering the non-tuberculous etiologies of chronic basal arachnoiditis like NCC before initiating therapy especially in countries endemic to both NCC and tuberculosis, like India.