Permissive Model Research Articles

Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats

Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH.

Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus

This study was aimed at investigating the possible involvement of the actin cytoskeleton in the modulation of host permissiveness to A/NWS/33 human influenza virus infection in two mammalian (MDCK and LLC-MK2) cell lines in vitro. During the early stages of infection, no appreciable association between incoming NWS/33 virions and cortical actin was detectable in the permissive MDCK model by confocal microscopy, while extensive colocalization and a slower infection progression were observed in LLC-MK2 cells. In the latter model, we also demonstrated the inability of the virus to carry out multiple replication cycles, irrespective of the presence of cleaved HA subunits in the released virions. Treatment with the actin-depolymerizing agent cytochalasin D significantly increased the infection efficiency in LLC-MK2 cells, while a detrimental effect was observed in the MDCK cell line. Our data suggest a selective role of the actin network in inducing a restriction to influenza virus replication, mostly depending on its molecular organization, the host cell type and virus replication phase.

What systems can and can't do

This commentary discusses a paper in this issue by Dr Jillian Baker on the antagonism of histamine H(2) receptors. It is an excellent example of the use of pharmacological principles to determine what systems can and can't do from the point of view of agonist-dependent antagonism. The most common model of antagonism, namely orthosteric, cannot discern agonist type; i.e. all agonists are blocked equally by a given orthosteric antagonist. Therefore, if quantitative assessment of antagonism unveils agonist dependence, then this is something an orthosteric mechanism cannot do and another mechanism must be considered. A simple alternative is a permissive allosteric model whereby the agonist and antagonist interact through conformational changes in the receptor protein. Under these circumstances, an agonist-antagonist dialogue can ensue whereby the nature of the agonist determines the magnitude of antagonist effect. Jillian Baker contrasts antagonist systems with historical data obtained for beta-adrenoceptors and the present data for histamine H(2) receptors where the simpler model of orthosteric antagonism suffices and thus shows how quantitative receptor pharmacology can be used to determine the molecular mechanism of antagonism.

A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease.

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.

A permissive geometry model for TCR–CD3 activation

The T cell antigen receptor (TCR-CD3) is the most complex receptor known to date, consisting of eight transmembrane subunits. Its activation by an antigen is the initial step in an immune response. Here, we present the permissive geometry model explaining how antigen binding initiates intracellular signalling cascades. We propose that a dimeric antigen imposes its geometry on two TCR-CD3 receptors by simultaneously binding to both. This causes the TCRalphabeta subunits to rotate with respect to each other leading to displacement of the ectodomains of the associated CD3 dimers. This results in a scissor-like movement of the CD3 dimers that opens the cytoplasmic tails for interaction with signalling proteins, thus initiating signalling cascades.

What counts as student voice in active citizenship case studies?

We analyse a teacher-to-teacher discourse (14 web-published case studies) concerning `participation as citizenship' in schools. Many different mechanisms through which pupils participate are reported (from school councils to paired-reading schemes and community links). The claimed outcomes of these activities are also varied: improving the effectiveness of schools, developing skills, and promoting feelings of involvement and empowerment among the participating pupils. Significantly, the outcomes are not radically or politically transformative and are generally contained within schools' existing structures. The texts reveal their adult authors' range of understandings of children and schooling, which help to explain the relatively conservative pattern of outcomes. However, the pattern is also explained, in part, by the contested interpretations of both participation and citizenship, and by the open and permissive model of education for citizenship favoured in Scotland.

The stoichiometry of the T cell antigen receptor and its implications for the signal transduction mechanism

AbstractThe T cell antigen receptor (TCR·CD3) is a multi‐subunit complex mediating T cell development and activation. The molecular mechanism of how this receptor transmits information across the membrane is still an enigma. The stoichiometry and architecture of this receptor in the membrane are under intense investigation, since they are important in deciphering the signal transduction mechanism of the TCR·CD3. This review highlights the evidence that TCR·CD3 is found on unstimulated T cells in monovalent (one ligand‐binding site per receptor) as well as in multivalent forms. Distinct detergents affect the integrity of the multivalent receptor differently, explaining controversial findings of TCR·CD3 stoichiometries as determined by biochemical means. The existence of multivalent receptors is not compatible with current models of TCR·CD3 triggering. Therefore, I discuss the novel “permissive geometry model” that combines multivalent TCR·CD3s, the requirement for multimeric ligands for receptor triggering and conformational changes at CD3.

Allosteric Changes in the TCR/CD3 Structure Upon Interaction With Extra‐ or Intra‐cellular Ligands

T lymphocytes are activated by the interaction between the T-cell antigen receptor (TCR) and peptides presented by major histocompatibility complex (MHC) molecules. The avidity of this TCR-pMHC interaction is very low. Therefore, several hypotheses have been put forward to explain how T cells become specifically activated despite this handicap: conformational change model, aggregation model, kinetic segregation model, sequential interaction model and permissive geometry model. In the present paper, we conducted experiments to distinguish between the TCR-aggregation model and the TCR-conformational change model. The results obtained using a TCR capture ELISA with Brij 98-solubilized TCR molecules from normal or activated T cells showed that the ligand-TCR interaction causes structural changes in the CD3 epsilon cytoplasmic tail as well as in the extracellular TCR beta FG loop region. Size-fractionation experiments with Brij 98-solubilized TCR/CD3/co-receptor complexes from naïve or activated CD4(+) or CD8(+) T cells demonstrated that such complexes are found as either dimers or tetramers. No monomers or multimers were detected. We propose that: (1) ligand-TCR interaction results in conformational changes in the CD3 epsilon cytoplasmic tail leading to T-cell activation; (2) CD3 epsilon cytoplasmic tail interaction with intracellular proteins may dissociate pMHC and co-receptors (CD4 or CD8) from TCR/CD3 complexes, thus leading to the arrest of T-cell activation; and (3) T-cell activation appears to occur among dimers or tetramers of TCR/CD3/co-receptor complexes interacting with self and non-self (foreign) peptide-MHC complexes.

Modelling the winter distribution of a rare and endangered migrant, the Aquatic Warbler Acrocephalus paludicola

The Aquatic Warbler Acrocephalus paludicola is one of the most threatened Western Palearctic passerine species, classified as globally Vulnerable. With its breeding grounds relatively secure, a clear need remains for the monitoring and protection of the migration and wintering grounds of this rare and endangered migrant. Recent research has shown that the Aquatic Warbler migrates through northwest Africa in autumn and spring. The wintering grounds are apparently limited to wetlands of sub‐Saharan West Africa, with records from only about 20 localities in Mauritania, Mali, Senegal and Ghana. Given the lack of knowledge of its whereabouts, we decided to use the available data to predict the wintering distribution of the Aquatic Warbler with the help of Geographic Information Systems (GIS). We used a novel approach to model the distribution of rarely recorded species, which is based on a combination of presence‐only and presence–absence modelling techniques. Using the program BIOMOD, we thus generated four progressively more conservative predictions of where the Aquatic Warbler overwinters in Africa. Whereas the most permissive model predicts the Aquatic Warbler to be found in a latitudinal band stretching from the Senegal river delta all the way to the Red Sea coast, the most restrictive model suggests a much smaller area concentrated within the regions around the Senegal river delta in northern Senegal and southern Mauritania and around the Niger inundation zone in southern Mali and eastern Burkina Faso. Such model predictions may be useful guidelines to focus further field research on the Aquatic Warbler. Given the excellent model predictions in this study, this novel technique may prove useful to model the distribution of other rare and endangered species, thus providing a means to guide future survey efforts.

The regulation of parathyroid hormone expression in thymus by Gcm2-dependent and Gcm2-independent pathways (B83)

Abstract The promiscuous gene expression of tissue-restricted self-antigens (TRA) in medullary thymic epithelial cells (mTEC) is required for the negative selection to establish the central tolerance. The mechanism of the promiscuous gene expression is still not clear. Two models have been proposed: Mosaic model proposed that many different tissue cells within the medulla express corresponding TRAs following the rules of tissue-specific regulation. Permissive model proposed that some mTECs can express TRAs differently compared to the tissue-specific regulation rules. Parathyroid hormone (Pth) is one of TRAs expressed in thymus. We explored the mechanism of the regulation of thymic Pth expression in mouse. We found the major thymic Pth expression was from some clusters of misplaced parathyroid cells. In Gcm2 null mutants, thymic Pth expression was greatly reduced due to the ablation of these misplaced parathyroid cells, suggesting a Gcm2-dependent pathway functioning in these cells. Using genetic marker technique, we sorted Foxn1-expressing TECs, and demonstrated that TECs were another source of thymic Pth expression. Thymic Pth expression level was similar in the purified TECs from Gcm2−/− and wildtype, suggesting this expression was regulated by a Gcm2-independent pathway. Our results support the permissive model. It will be interesting to know if this mechanism is also used by other TRAs.

Full Activation of the T Cell Receptor Requires Both Clustering and Conformational Changes at CD3

T cell receptor (TCR-CD3) triggering involves both receptor clustering and conformational changes at the cytoplasmic tails of the CD3 subunits. The mechanism by which TCRalphabeta ligand binding confers conformational changes to CD3 is unknown. By using well-defined ligands, we showed that induction of the conformational change requires both multivalent engagement and the mobility restriction of the TCR-CD3 imposed by the plasma membrane. The conformational change is elicited by cooperative rearrangements of two TCR-CD3 complexes and does not require accompanying changes in the structure of the TCRalphabeta ectodomains. This conformational change at CD3 reverts upon ligand dissociation and is required for T cell activation. Thus, our permissive geometry model provides a molecular mechanism that rationalizes how the information of ligand binding to TCRalphabeta is transmitted to the CD3 subunits and to the intracellular signaling machinery.

Obligatory Role for Interleukin-13 in Obstructive Lesion Development in Airway Allografts

The pathogenesis of bronchiolitis obliterans (BO), a common and devastating obliterative disorder of small airways following lung transplantation, remains poorly understood. Lesions are characterized in their early stages by lymphocyte influx that evolves into dense fibrotic infiltrates. Airway specimens taken from patients with histological BO revealed infiltrating myofibroblasts, which strongly expressed the signaling chain of the high affinity interleukin-13 (IL-13) receptor IL-13Ralpha1. Because IL-13 has proinflammatory and profibrotic actions, a contributory role for IL-13 in BO development was examined using murine models of orthotopic and heterotopic tracheal transplantation. Compared with airway isografts, allografts exhibited a significant increase in relative IL-13 mRNA and protein levels. Allogeneic tracheas transplanted into IL-13-deficient mice were protected from BO in both transplant models. Flow cytometric analysis of orthotopic transplant tissue digests revealed markedly fewer infiltrating mononuclear phagocytes and CD3(+) T lymphocytes in IL-13-deficient recipients. Furthermore, protection from luminal obliteration, collagen deposition, and myofibroblast infiltration was observed in heterotopic airways transplanted into the IL-13(-/-) recipients. Transforming growth factor-beta1 expression was significantly decreased in tracheal allografts into IL-13(-/-) recipients, compared to wild-type counterparts. These human and murine data implicate IL-13 as a critical effector cytokine driving cellular recruitment and subsequent fibrosis in clinical and ex-perimental BO.

Syrian Hamster as a Permissive Immunocompetent Animal Model for the Study of Oncolytic Adenovirus Vectors

Oncolytic adenoviruses represent an innovative approach to cancer therapy. These vectors are typically evaluated in immunodeficient mice with human xenograft tumors. However, in addition to being immunodeficient, this model is limited because normal and cancerous mouse tissues are poorly permissive for human adenovirus replication. This prompted us to search for a model that more accurately reflects the use of oncolytic adenoviruses in cancer patients. To this end, we developed a novel Syrian hamster model that is both immunocompetent and replication-permissive. We found that human adenovirus replicates well in Syrian hamster cell lines and confirmed replication in the lungs. Oncolytic adenovirus injection showed efficacy in three different hamster tumor models. Furthermore, i.t. oncolytic adenovirus injection resulted in suppression of primary and metastatic lesions, i.t. replication and necrosis, vector entrance into the bloodstream, replication in the liver and lungs, and anti-adenovirus antibody induction. Our findings show that the Syrian hamster is a promising immunocompetent model that is permissive to human adenovirus replication in tumors as well as normal tissues. Therefore, the Syrian hamster model may become a valuable tool for the field of oncolytic adenovirus vectors in which vector safety and efficacy can be evaluated.

A METHODOLOGY TO DESIGN AND CHECK A PLANT MODEL

Applications on manufacturing systems (diagnosis, control, supervision…) often require a plant model. Obtaining the plant model is a difficult task because of systems complexity and deepth knowledge of physical materials. A necessary condition that must be verified by the plant model is its capability to respond to all the requests of the specification model. This paper ends by two complementary approaches a mathematical property is proposed to check formally and this capability and a methodology to design the plant model is proposed in order to guarantee the model capability according to the most permissive control model.

A hybrid approach to supervisory control of discrete event systems coupling RW supervisors to Petri nets

In this paper a hybrid approach is proposed for supervisory control of discrete event systems (DES) subject to forbidden states. Assuming that an uncontrolled bounded Petri net (PN) model of a (plant) DES and a set of forbidden state specifications are given, the proposed approach computes a maximally permissive and nonblocking closed-loop hybrid model. The first step is to simplify the given PN model by means of PN reduction rules. The simplified model and the specifications are then represented as buffers, and supervisory control theory (SCT) is applied to obtain a Ramadge–Wonham (RW) supervisor in the form of an automaton. After reduction of the latter’s state size by a ‘control congruence’, the simplified RW supervisor is represented by a so-called auto-net and coupled to the given uncontrolled PN plant model by means of inhibitor arcs to represent the disabling actions. The plant model and supervisor auto-net run concurrently, synchronizing on shared events. This procedure provides a maximally permissive and nonblocking ‘hybrid’ (mixed PN/automaton) closed-loop controlled system. The method is straightforward logically, graphically, and technologically. Its applicability is shown by two examples, one of them a workcell from the PN control literature.

The Cotton Rat ( Sigmodon hispidus ) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity

Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 x 10(2) PFU/gram tissue (C3H mice) to greater than 10(5) PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 x 10(5) PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.

Reciprocal regulation of airway rejection by the inducible gas-forming enzymes heme oxygenase and nitric oxide synthase

Obliterative bronchiolitis (OB) develops insidiously in nearly half of all lung transplant recipients. Although typically preceded by a CD8+ T cell–rich lymphocytic bronchitis, it remains unresponsive to conventional immunosuppression. Using an airflow permissive model to study the role of gases flowing over the transplanted airway, it is shown that prolonged inhalation of sublethal doses of carbon monoxide (CO), but not nitric oxide (NO), obliterate the appearance of the obstructive airway lesion. Induction of the enzyme responsible for the synthesis of CO, heme oxygenase (Hmox) 1, increased carboxyhemoglobin levels and suppressed lymphocytic bronchitis and airway luminal occlusion after transplantation. In contrast, zinc protoporphyrin IX, a competitive inhibitor of Hmox, increased airway luminal occlusion. Compared with wild-type allografts, expression of inducible NO synthase (iNOS), which promotes the influx of cytoeffector leukocytes and airway graft rejection, was strikingly reduced by either enhanced expression of Hmox-1 or exogenous CO. Hmox-1/CO decreased nuclear factor (NF)-κB binding activity to the iNOS promoter region and iNOS expression. Inhibition of soluble guanylate cyclase did not interfere with the ability of CO to suppress OB, implicating a cyclic guanosine 3′,5′-monophosphate–independent mechanism through which CO suppresses NF-κB, iNOS transcription, and OB. Prolonged CO inhalation represents a new immunosuppresive strategy to prevent OB.

Impaired Transporter Associated with Antigen Processing-Dependent Peptide Transport during Productive EBV Infection

Human herpesviruses, including EBV, persist for life in infected individuals. During the lytic replicative cycle that is required for the production of infectious virus and transmission to another host, many viral Ags are expressed. Especially at this stage, immune evasion strategies are likely to be advantageous to avoid elimination of virus-producing cells. However, little is known about immune escape during productive EBV infection because no fully permissive infection model is available. In this study, we have developed a novel strategy to isolate populations of cells in an EBV lytic cycle based on the expression of a reporter gene under the control of an EBV early lytic cycle promoter. Thus, induction of the viral lytic cycle in transfected EBV(+) B lymphoma cells resulted in concomitant reporter expression, allowing us, for the first time, to isolate highly purified cell populations in lytic cycle for biochemical and functional studies. Compared with latently infected B cells, cells supporting EBV lytic cycle displayed down-regulation of surface HLA class I, class II, and CD20, whereas expression levels of other surface markers remained unaffected. Moreover, during lytic cycle peptide transport into the endoplasmic reticulum, was reduced to <30% of levels found in latent infection. Because steady-state levels of TAP proteins were unaffected, these results point toward EBV-induced interference with TAP function as a specific mechanism contributing to the reduced levels of cell surface HLA class I. Our data implicate that EBV lytic cycle genes encode functions to evade T cell recognition, thereby creating a window for the generation of viral progeny.

1023. Determination of the Maximum Tolerated Dose of the Replication-Competent Adenovirus Vector VRX-007 Following Intravenous Administration in Syrian Hamsters

We have developed the Syrian hamster as a permissive immunocompetent model to evaluate the safety and efficacy of replication-competent adenovirus (Ad) vectors for cancer gene therapy. One of our vectors is named VRX-007; VRX-007 overexpresses ADP, an Ad protein that mediates virus release and cell-to-cell spread. In order to determine the maximum tolerated dose (MTD) of VRX-007 in hamsters, we administered a single injection of VRX-007 into the jugular vein. Hamsters received 1.9 |[times]| 108 PFU, 1.9 |[times]| 109 PFU, or 1.9 |[times]| 1010 PFU. No morbidity and no gross or histopathologic abnormalities were observed. In a second study, we administered VRX-007 via the jugular vein on three consecutive days. The cumulative doses were 1.9 |[times]| 1010 PFU for the low dose group, 5.7 |[times]| 1010 PFU for the intermediate dose group, and 1.1 |[times]| 1011 PFU for the high dose group. Half of each group was sacrificed on day 4, and the remainder of the animals were sacrificed on day 14. Hamsters in the low dose group did not display signs of morbidity, and no significant findings were observed grossly at either sacrifice date. In the intermediate group, one animal died on day 7; at necropsy, there was mild to moderate gross liver pathology at day 4 but only mild liver pathology at day 14. All animals in the high dose group were either found dead or became moribund and were sacrificed by three days postinjection. Liver enzymes (ALT and AST) in the serum were measured in order to evaluate the degree of hepatotoxicity. These enzymes were normal in the low dose group. For the intermediate group, the ALT and AST levels generally correlated with the degree of gross liver pathology observed at necropsy, with mild to moderate elevation at 4 days that resolved at 14 days. For the low and intermediate groups, elevation of alkaline phosphatase levels as well as a decrease in total protein and albumin levels were observed at 4 but not 14 days. For both groups, hematological analysis revealed a dose-dependent decrease in platelet counts on day four, although platelet counts were normal again at 14 days. Based on these data, we estimate the MTD of VRX-007 when adminstered intravenously on three consecutive days into Syrian hamsters to be the low dose used in this study (1.9 |[times]| 1010 PFU total or 1.7 |[times]| 1011 VP total). This corresponds to a dose of 2.1 |[times]| 1011 PFU/kg (1.9 |[times]| 1012 VP/kg).

Infrared imaging of compositional changes in inflammatory cardiomyopathy

Myocarditis is an inflammatory disorder that affects heart muscle cells and results in their dysfunction. The group B coxsackieviruses are the most common agents of myocarditis. In most cases the disease is self-limiting; however, idiopathic dilated cardiomyopathy may in many instances represent the end stage of an immunologically mediated disease initiated by an episode of enteroviral myocarditis. Studies indicated that inflammatory dilated cardiomyopathy accounts for about 25% of the cases of heart failure in the United States. Earlier studies on a cardiomyopathic Syrian hamster model have shown that extracellular matrix remodeling plays a significant role in the cardiac dysfunction [I.M. Dixon, H. Ju, N.L. Reid, T. Scammell-La Fleur, J.P. Werner, G. Jasmin, J. Mol. Cell. Cardiol. 29 (7) (1997) 1837–1850] and previous FTIR microspectroscopy studies demonstrated elevated fibrillar collagen in the pathological myocardium [K.M. Gough, D. Zelinski, R. Wiens, M. Rak, I.M. Dixon, Anal. Biochem. 316 (2) (2003) 232–242]. The aim of this study was to investigate the chemical composition of the myocardium in an immuno-resistant (C57BL/6) and an immuno-permissive (ABY/SnJ) mouse model of cardiomyopathy, using Fourier transform infrared imaging (FTIRI). Cross-sections (8 μm thick) of heart muscle tissue from murine CVB-models were acquired at 4, 8, and 28 days post-inoculation with the virus, mounted on infrared-reflective glass slides, and FTIRI was performed ( n = 2 for each stage). Age-matched controls were also examined ( n = 3). The composition and distribution of proteins and lipids were obtained at a pixel resolution of 6.25 μm. Specifically, the lipid/protein ratio (area ratio of 3000–2800/1700–1600 cm −1) and the collagen content (correlation analysis from 1400 to 1000 cm −1) were determined. Results from both mouse models showed that the lipid/protein ratio decreased as the collagen content increased, suggesting extracellular matrix remodeling. In the permissive model (ABY/SnJ), the lipid/protein ratio decreased and the collagen content increased continuously as the disease progressed. However, in the resistant model (C57BL/6), the lipid/protein ratio decreased and the collagen content increased in the early stages of the disease (4 and 8 days), but then reversed in the later stages (28 days), suggesting a recovery from the disease. These results demonstrate chemical differences between the inflammatory responses in these two mouse models, providing insight into why the disease can be self-limiting in some cases while fatal in others.