Chronic virus infection drives CD8 T cell-mediated thymic destruction and impaired negative selection.

Chronic infection provokes alterations in inflammatory and suppressive pathways that potentially affect the function and integrity of multiple tissues, impacting both ongoing immune control and restorative immune therapies. Here we demonstrate that chronic lymphocytic choriomeningitis virus infection rapidly triggers severe thymic depletion, mediated by CD8 T cell-intrinsic type I interferon (IFN) and signal transducer and activator of transcription 2 (Stat2) signaling. Occurring temporal to T cell exhaustion, thymic cellularity reconstituted despite ongoing viral replication, with a rapid secondary thymic depletion following immune restoration by anti-programmed death-ligand 1 (PDL1) blockade. Therapeutic hematopoietic stem cell transplant (HSCT) during chronic infection generated new antiviral CD8 T cells, despite sustained virus replication in the thymus, indicating an impairment in negative selection. Consequently, low amounts of high-affinity self-reactive T cells also escaped the thymus following HSCT during chronic infection. Thus, by altering the stringency and partially impairing negative selection, the host generates new virus-specific T cells to replenish the fight against the chronic infection, but also has the potentially dangerous effect of enabling the escape of self-reactive T cells.

Bursa atrophy at 28 days old caused by variant infectious bursal disease virus has a negative economic impact on broiler farms in Japan.

Infectious bursal disease (IBD), caused by IBD virus (IBDV), is highly contagious, immunosuppressive and causes a negative economic impact on poultry industry. IBDV-vaccinated broiler farms at south Kyushu, Japan had a bursa-to-bodyweight ratio (BB ratio) reduction at 28 days (d) old, followed by high mortality 30 d later. We analysed the influence of the IBDV on atrophy of the bursa of fabricius (BF) and the subsequent mortality after 30 d. Ten broilers were sampled at each timepoint from the farm with high mortality at 21, 25, 28 and 35 d. A second flock from the same farm was sampled at 14, 21, 25, 28, 35 and 42 d. IBDV was detected in BF samples at 25, 28 and 35 d and at 21, 25, 28 and 35 d in the first and second flocks, respectively, using immunohistochemical staining and RT-PCR. IBDV isolates from both flocks were closely related to the China KM523643 strain. Histopathology and TUNEL assay indicated apoptosis, severe lymphoid depletion, vacuoles within follicles, lymphoid follicle atrophy and fibrosis in the BF. We observed 75% of the polyserositis and 10% of the airsacculitis at 30 D in dead broilers. The antigenic variant IBDV infection was appeared to be the main influencing factor on BF atrophy and BB ratio reduction in the broilers. High mortality in the broilers after 30 d could be due to secondary infection. The disease caused by IBDV had a negative economic impact in the farm. RESEARCH HIGHLIGHTS New variant IBDV caused bursa atrophy and reduced BB ratio in 28-day-old broilers. After vIBDV had infected broilers, at 21 days old they became immunosuppressed. High mortality at 30 days old in broilers was due to secondary infection. New vIBDV has a negative economic impact on broiler farms in Japan.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Progressive brain atrophy in chronically infected and treated HIV+ individuals.

Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.

Atrophy of primary lymphoid organs induced by Marek's disease virus during early infection is associated with increased apoptosis, inhibition of cell proliferation and a severe B-lymphopenia.

Marek's disease is a multi-faceted highly contagious disease affecting chickens caused by the Marek's disease alphaherpesvirus (MDV). MDV early infection induces a transient immunosuppression, which is associated with thymus and bursa of Fabricius atrophy. Little is known about the cellular processes involved in primary lymphoid organ atrophy. Here, by in situ TUNEL assay, we demonstrate that MDV infection results in a high level of apoptosis in the thymus and bursa of Fabricius, which is concomitant to the MDV lytic cycle. Interestingly, we observed that in the thymus most of the MDV infected cells at 6 days post-infection (dpi) were apoptotic, whereas in the bursa of Fabricius most of the apoptotic cells were uninfected suggesting that MDV triggers apoptosis by two different modes in these two primary lymphoid organs. In addition, a high decrease of cell proliferation was observed from 6 to 14 dpi in the bursa of Fabricius follicles, and not in the thymus. Finally, with an adapted absolute blood lymphocyte count, we demonstrate a major B-lymphopenia during the two 1st weeks of infection, and propose this method as a potent non-invasive tool to diagnose MDV bursa of Fabricius infection and atrophy. Our results demonstrate that the thymus and bursa of Fabricius atrophies are related to different cell mechanisms, with different temporalities, that affect infected and uninfected cells.

NK-cells are involved in thymic atrophy induced by influenza A virus infection.

NK-cells have traditionally been viewed as innate effector lymphocytes that serve as a first line of defence against a range of viruses and tumours. More recently, the importance of NK-cell immunoregulatory functions has been highlighted. NK-cells can inhibit antiviral T-cell responses, and also play an important role in controlling harmful T-cell activity in autoimmunity and transplantation settings. Moreover, immunopathological effects of NK-cells during infection have been reported. Nevertheless, the phenotype and function of NK-cells in the thymus during influenza virus infection is not understood. In the present study, we demonstrated that influenza A virus (IAV) infection in mice led to severe thymic atrophy caused by increased thymic T-cell apoptosis and suppressed proliferation. We found that NK-cells played a critical role in this phenotype. IFN-c production by NK-cells was a contributing factor for thymic atrophy during IAV infection. Taken together, our data indicate that NK-cells are involved in the thymic atrophy associated with IAV infection.

Voluma: A Systematic Review of Clinical Experience.

BACKGROUND: Dermal fillers are important for facial aesthetic enhancement as patients are favoring non-surgical procedures with minimal recovery time. Voluma is a volumizing hyaluronic acid filler, 20 mg/ml HA dermal filler, which was FDA-approved in 2013 as the first dermal filler for treatment of age-related volume loss in the midface. OBJECTIVE: We sought to systematically review clinical studies and expert opinions of this 20 mg/ml HA dermal filler and to provide evidence-based recommendations and expert opinions. METHODS AND MATERIALS: A search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts was performed on August 18th 2014. RESULTS: Thirteen articles met inclusion and were included in our review: clinical trials with this 20 mg/ml HA dermal filler (10) and expert opinions and questionnaire survey studies of experts (3). This 20 mg/ml HA dermal filler has shown consistent, favorable results for treatment of age-related facial volume loss, aesthetic enhancement, and HIV facial lipoatrophy. CONCLUSION: HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes.

A novel birnavirus identified as the causative agent of summer atrophy of pearl oyster (Pinctada fucata (Gould)).

The Akoya pearl oyster (Pinctada fucata (Gould)) is the most important species for pearl cultivation in Japan. Mass mortality of 0-year-old juvenile oysters and anomalies in adults, known as summer atrophy, have been observed in major pearl farming areas during the season when seawater temperatures exceed about 20 °C since 2019. In this study, we identified a novel birnavirus as the pathogen of summer atrophy and named it Pinctada birnavirus (PiBV). PiBV was first presumed to be the causative agent when it was detected specifically and frequently in the infected oysters in a comparative metatranscriptomics of experimentally infected and healthy pearl oysters. Subsequently, the symptoms of summer atrophy were reproduced by infection tests using purified PiBV. Infection of juvenile oysters with PiBV resulted in an increase in the PiBV genome followed by the atrophy of soft body and subsequent mortality. Immunostaining with a mouse antiserum against a recombinant PiBV protein showed that the virus antigen was localized mainly in the epithelial cells on the outer surface of the mantle. Although the phylogenetic analysis using maximum likelihood method placed PiBV at the root of the genus Entomobirnavirus, the identity of the bi-segmented, genomic RNA to that of known birnaviruses at the full-length amino acid level was low, suggesting that PiBV forms a new genus. The discovery of PiBV will be the basis for research to control this emerging disease.

HIV-associated facial lipoatrophy treated with injectable silicone oil: a pilot study.

BACKGROUND: Facial lipoatrophy (FLA) is associated with HIV infection and is part of the lipodystrophy syndrome. Temporary filler treatments do not meet the need of the patient, as there is a lack of permanence, and excessive cost. OBJECTIVE: We sought to evaluate the safety and efficacy of a highly purified medical-grade 1000-cst liquid injectable silicone in the treatment of HIV-associated FLA using the serial microdroplet injection technique. METHODS: Twenty patients with HIV-associated lipoatrophy were treated with liquid injectable silicone with a maximum of 6 treatment sessions (2.0 mL each session maximum). Patients were evaluated at 9-, 12-, and 18-month follow-up sessions. Safety, efficacy, injection volumes, and patient satisfaction were evaluated. RESULTS: No persistent adverse effects were reported throughout the study. Most of the patients achieved complete correction of their HIV-associated FLA after 6 treatments and maintained this correction to the 18-month follow-up. LIMITATIONS: This is a noncomparative, nonblinded study. Study patient population size is small. CONCLUSION: Given our small sample size of 20 patients, our results suggest that, if administered correctly, liquid injectable silicone is potentially a safe, effective, and natural-feeling treatment option for HIV-associated FLA. Larger studies may be needed to confirm safety, efficacy, and permanence.

Properties of a meq-deleted rmd5 Marek's disease vaccine: protection against virulent MDV challenge and induction of lymphoid organ atrophy are simultaneously attenuated by serial passage in vitro.

We have previously shown that deletion of the meq gene from the genome of Cosmid-cloned rMd5 strain of Marek's disease virus (MDV-1) resulted in loss of transformation and oncogenic capacity of the virus. The rMd5deltaMeq (Meq null) virus has been shown to be an excellent vaccine in maternal antibody positive (MAb+) chickens challenged with a very virulent plus (vv+) strain of MDV, 648A. The only drawback was that it retained its ability to induce bursa and thymus atrophy (BTA) like that of the parental rMd5 in maternal antibody negative (MAb-) chickens. We recently reported that the attenuated Meq null virus did not induce BTA at the 40th cell culture passage onward. Its protective ability against challenge with vv+ MDV, strain 686 was similar to the original virus at the 19th passage in MAb- chickens. In this study, we compared the same series of attenuated meq null viruses in commercial chickens. In commercial chickens with MAb, the attenuated viruses quickly lost protection with increasing cell culture attenuation. These data suggest that although attenuation of these meq null viruses eliminated BTA, it had no influence on their protective efficacy in MAb- chickens. However, in commercial chickens (MAb+), the best protection was provided by the original 19th passage; the attenuated 40th passage was as good as one of the currently commercial CVI988/Rispens vaccine, and it did not induce BTA. Therefore, protection against virulent MDV challenge and induction of lymphoid organ atrophy are simultaneously attenuated by serial passage in vitro.

Clinical and neuroimaging profile of HIV-1 encephalopathy in infancy and childhood in a sub-Saharan African country.

BACKGROUND: Neurological dysfunction in AIDS is common, occurring in as many as eighty percent of children. Thus, it is important to recognize the central nervous system imaging appearance of HIV, in particular those of HIV encephalopathy, as this is an AIDS defining illness and with distinct neuro-imaging features essential for early diagnosis and timely therapeutic intervention AIM: To identify the clinical features in HIV-1 infection of the central nervous system and their associated neuroradiological correlates. METHODS: Retrospective review of the records of all children with HIV-1 encephalopathy identified among children with neurological and developmental problems and who were on follow up at a child development and neurology clinic in an African city. RESULTS: A total of 22 children (10 male and 12 female) with HIV-1 encephalopathy were identified among 2382 children with various forms of neurological and developmental problems and who were on follow up at a child development and neurology clinic for a little bit over eight years period. All the children acquired the infection vertically. The age range of these children was between 10 months to 14 years. The median age was 5.6 years. The mean duration of symptom was 3.2 years. Global delay or regression in development along with signs of pyramidal tract involvement and seizures were the commonest clinical signs observed in these children. Neuro-behavioral problems were commonly observed among preschool and school aged children. In older children and preadolescents focal seizures with or with out neurologic deficit and neuroradiological findings were common. Nonhemorrhagic stroke was rare and occurred in one child and another child had cortical blindness. Three children had no neurological deficit. Rapid progression of the disease carried grave prognosis. Opportunistic infections and tumors of the central nervous system were also uncommon among these children. Brain volume loss with dilatation of the lateral ventricle, bilateral symmetrical or asymmetrical calcification of the basal ganglia and periventricular involvement of the white matter were the commonest neuro-radiological findings observed in these children. CONCLUSION: Atrophy of the brain with dilatation of the lateral ventricles and calcification of the basal ganglia and peri-ventricular involvement of the white matter were the commonest neuro-radiological findings in children with HIV-1 encephalopathy. Similarly global delay or regression in development along with pyramidal tract signs and seizures were the commonest neurological findings. Behavioral problems were common in preschool and school aged children. Focal seizures were common in older children and preadolescents. Rapid progression of the disease carried grave prognosis.

Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection.

Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/ß expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNαßR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers.

Effect of human immunodeficiency virus on the brain: A review.

Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV-associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV-positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.

Two patients with acute rotavirus encephalitis associated with cerebellar signs and symptoms.

Rotavirus, one of the major causes of severe gastroenteritis in children, occasionally causes central nervous system complications. Recently several patients with acute encephalitis/encephalopathy due to rotavirus associated with cerebellar signs and symptoms have been reported. The condition is characterized by disturbances of consciousness at onset and cerebellar signs and symptoms such as hypotonia, ataxia, dysmetria, and speech disorders, including mutism, slow speech, and dysarthria at convalescence. We report two patients (3-year-old girl, 2-year-old boy) who developed acute encephalitis due to rotavirus and showed cerebellar signs and symptoms. Both patients had characteristic history of consciousness disturbances subsequent to several days of diarrhea, vomiting and fever, and cerebellar symptoms such as hypotonia, ataxia, dysmetria, and speech disorders during the recovery period. Electroencephalography showed diffuse high-voltage delta wave activity in each patient. Brain magnetic resonance imaging showed cerebellar edema in the acute phase followed by cerebellar atrophy on follow-up images in both patients. In the first patient, diffusion-weighted images (DWI) revealed high signals at the left cerebellar peduncle region and apparent diffusion coefficient (ADC) maps showed decreased ADC values of the lesion in the acute phase. The first patient had dysmetria at 1-year follow-up. However, she had normal motor and cognitive functions and could lead her daily life without impairment. In the second patient, no further symptoms were apparent at 1-year follow-up. Acute encephalitis/encephalopathy due to rotavirus with cerebellar signs and symptoms might be diagnosed on DWI, by demonstrating decreased ADC values in acute phase.

Serum matrix metalloproteinase levels correlate with brain injury in human immunodeficiency virus infection.

Circulating levels of specific matrix metalloproteinases (MMPs; 1 and 7) were evaluated as correlates of brain injury in eight individuals in advanced human immunodeficiency virus (HIV) infection. Neurological status was quantified in vivo with automated segmentation algorithms and with diffusion tensor imaging. Both metalloproteinases correlated with microstructural brain alterations and the degree of atrophy. MMPs may influence neurological outcome through involvement in neuroimmune response, blood-brain barrier permeability, leukocyte migration, and MMP-mediated neurotoxicity.

Infection with a pathogenic turkey coronavirus isolate negatively affects growth performance and intestinal morphology of young turkey poults in Canada.

Turkey coronavirus (TCoV) is an important viral pathogen causing diarrhoea of young turkey poults that is associated with sizeable economic losses for the turkey industry. Using a field isolate that was found to be free from turkey astrovirus and avian reovirus we were able to reproduce the clinical disease associated with TCoV. Clinical signs and weight gain of poults during experimental infections were compared with age-matched, uninfected controls. Poults infected at 2 days of age had 100% morbidity and 10% mortality, and birds infected at 28 days of age showed 75% morbidity and no mortality. Diarrhoea was consistently seen in infected poults at 2 to 3 days post infection (d.p.i.) with a duration of about 3 to 5 days. Mean body weights of birds infected at 2 or 28 days of age were significantly reduced compared with uninfected birds by 7 d.p.i. and remained significantly lower for the duration of the study. At 44 days of age, poults infected at 2 or 28 days of age weighed only 68.1% or 77.7%, respectively, compared with uninfected turkeys of the same age on the same diet, a mean difference in body weights of 683 or 477g, respectively. Infected birds had profound villus atrophy with some compensatory crypt hyperplasia at 5 to 7 d.p.i. Villus heights in the duodenum were significantly reduced at 7 d.p.i. We were able to reproduce enteric disease using only a pathogenic field isolate (MG10) of TCoV that negatively affected growth performance and intestinal morphology of young turkey poults.

Cross-species infectivity and pathogenesis of the Friend murine leukemia virus complex in Syrian hamsters.

To investigate cross-species infectivity and pathogenesis of Friend murine leukemia virus (MuLV) in hamsters, we infected newborn Syrian hamsters with ecotropic Friend MuLV that was passaged in BALB/c mice for approximately 30 years. During acute infection, 39.5% of newborn Syrian hamsters developed severe growth interruption and weight loss, spleen atrophy, severe lymphocyte depletion, and massive viral antigen loads in the spleen. The lymph nodes and thymuses were observed in all diseased hamsters. Ecotropic Friend MuLV was rescued from the sera and spleen and heart extracts of the diseased hamsters, and the same disease was confirmed by induction of erythroleukemia in BALB/c mice. Our results demonstrate that an ecotropic MuLV after extended passage in vivo to infect hamster cells that are resistant to infection by wild type MuLV, causing pathologic lesions and a wasting syndrome in newborn hamsters in vivo. This may occur with variants of Friend MuLV that have lower infectivity in hamster cells and are not cleared by the immune system of newborn hamsters. These findings suggest the potential danger of the interspecies transmission and pathogenesis of heterologous retroviruses in humans.

[Late consequences of hemorrhagic fever with renal syndrome in a woman who had it during pregnancy].

The authors adduce a brief description of the features and outcomes of hemorrhagic fever with renal syndrome (HFRS) in 8 pregnant women. The results of the examination of a 54-year-old woman and her son, who suffered from a severe form of HERS 28 years ago during the 31st week of pregnancy, are presented in detail. Antibodies to Hantaan virus 1:32 were found; magnetic resonance tomography of the skull revealed sequelae of hypophysial hemorrhage with the formation of "partly empty ephippium". The antibodies were not found in the son; hydrocephalus, forehead cortex atrophy, and lateral ventricular asymmetry were revealed.

Transcranial magnetic stimulation. A case report and review of the literature.

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. CASE REPORT: A 2-years-old male infant was referred to our department with a history of Epstein-Barr virus (EBV) encephalitis, treated with foscarnet and steroids, for he developed mutism and ataxia and loss of the ability to eat, walk and talk. Brain imaging revealed loss of white matter around ventricles and progressive global brain atrophy, findings consistent with encephalopathy. Serology for antibodies against EBV infection was positive and the diagnosis of acute and prolonged EBV infection was made. There was an improvement of the clinical findings after the application of TMS with proper field characteristics (intensity: 1-7.5 pT, frequency: 8-13 Hz). CONCLUSIONS: Our case illustrates the possibility of therapeutic applications of TMS (in the order of pT) with proper field characteristics to normalize pathologically decreased levels of brain cortex activity. TMS might provide novel insights into the pathophysiology of the neural circuitry, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases.

Thymic depletion of lymphocytes is associated with the virulence of PRRSV-1 strains.

Porcine reproductive and respiratory syndrome virus (PRRSV) exists as two distinct viruses, type 1 (PRRSV-1) and type 2 (PRRSV-2). Atrophy of the thymus in PRRSV-2 infected piglets has been associated with a loss of thymocytes. The present study aimed to evaluate the impact of PRRSV-1 strains of differing virulence on the thymus of infected piglets by analysing the histomorphometry, the presence of apoptotic cells and cells producing cytokines. Thymic samples were taken from animals experimentally infected (with LV, SU1-bel, and 215-06 strains) or mock inoculated animals at 3, 7 and 35days post-infection (dpi) and processed for histopathological and immunohistochemical analyses. PRRSV antigen was detected in the thymus from 3dpi until the end of the study in all virus-infected animals with the highest numbers of infected cells detected in SU1-bel group. The histomorphometry analysis and counts of CD3(+) thymocytes in the thymic cortex displayed significant differences between strains at different time-points (p≤0.011), with SU1-bel group showing the most severe changes at 7dpi. Cell death displayed statistically significant increase in the cortex of all infected animals, with SU1-bel group showing the highest rate at 3 and 7dpi. The number of cells immunostained against IL-1α, TNF-α and IL-10 were predominantly detected in the medulla (p≤0.01). An increase in the number of TNF-α and IL-10 positive cells was observed in LV and SU-1bel groups. Our results demonstrate that different PRRSV-1 strains induced depletion of the thymic cortex due to apoptosis of thymocytes and that the most severe depletion was associated with the highly virulent SU1-bel strain.