Secondary Viremia Research Articles

Viral modulation of type II interferon increases T cell adhesion and virus spread

During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.

Kaposi's Varicelliform Eruption: A Potentially Life-Threatening Complication of Atopic Dermatitis.

Kaposi's varicelliform eruption (KVE), also known as eczema herpeticum or eczema vaccinatum, is an acute dermatosis that affects patients with chronic dermatopathies. The diagnosis is primarily clinical and is characterised by the presence of a vesicular exanthema on physical examination. The exanthema subsequently evolves into crusted lesions with typical circular ulcerations in 'punched-out' areas on the skin affected by the underlying dermatopathy. We present the case of a 6-year-old patient who presented to the Paediatric Emergency department with skin lesions consistent with eczema herpeticum. The patient's management was initially outpatient; however, due to the slow progression of the condition, hospitalisation and intravenous antiviral treatment were initiated. KVE affects patients with chronic dermatoses, especially atopic dermatitis. It is important to know the clinical presentation for an early suspicion. KVE is a medical emergency that requires prompt diagnosis and treatment. It can progress to secondary viraemia, which can be fatal in up to 10% of immunocompetent individuals and up to 50% of immunocompromised individuals. It is important to be aware of this condition and to start early treatment with antivirals, especially given the high prevalence of atopic dermatitis in our population. This condition is one of the most serious complications that can occur in these patients. To facilitate early suspicion and diagnosis, disseminate information about eczema vaccinatum.Emphasise the importance of initiating antiviral treatment early to prevent potential complications of eczema herpeticum.If left untreated, Kaposi's varicelliform eruption can result in up to a 10% mortality rate in immunocompetent individuals and a 50% mortality rate in those who are immunocompromised.

Polycytidine tract deletion from microRNA-detargeted oncolytic Mengovirus optimizes the therapeutic index in a murine multiple myeloma model

Mengovirus is an oncolytic picornavirus whose broad host range allows for testing in immunocompetent cancer models. Two pathogenicity-ablating approaches, polycytidine (polyC) tract truncation and microRNA (miRNA) targets insertion, eliminated the risk of encephalomyocarditis. To investigate whether a polyC truncated, miRNA-detargeted oncolytic Mengovirus might be boosted, we partially or fully rebuilt the polyC tract into the 5' noncoding region (NCR) of polyC-deleted (MC0) oncolytic constructs (NC) carrying miRNA target (miRT) insertions to eliminate cardiac/muscular (miR-133b and miR-208a) and neuronal (miR-124) tropisms. PolyC-reconstituted viruses (MC24-NC and MC37-NC) replicated invitro and showed the expected tropism restrictions, but reduced cytotoxicity and miRT deletions were frequently observed. In the MPC-11 immune competent mouse plasmacytoma model, both intratumoral and systemic administration ofMC0-NC led to faster tumor responses than MC24-NC or MC37-NC, with combined durable complete response rates of 75%, 0.5%, and 30%, respectively. Secondary viremia was higher following MC0-NC versus MC24-NC or MC37-NC therapy. Sequence analysis of virus progeny from treated mice revealed a high prevalence of miRT sequences loss among MC24- and MC37- viral genomes, but not in MC0-NC. Overall, MC0-NC was capable of stably retaining miRT sites and provided a more effective treatment and is therefore our lead Mengovirus candidate for clinical translation.

Measles: A Review

Measles is an acute febrile viral illness of children. It is highly contagious and its incidence has decreased significantly following successful use of vaccine. The measles immunity following vaccination or natural infection is long lasting. The causative virus is highly transmissible aerogenously or by direct contact. The virus affects lympho-reticular systems. The secondary viraemia causes fever coryza cough and conjunctival redness. Erythematous maculopapular rash helps in diagnosing the condition clinically. The condition is selflimiting. However pneumonia encephalitis subacute sclerosing pan encephalitis and death may occur as complications. Vitamin A and antibiotic prophylaxis reduces the morbidity. Measles vaccine prepared from attenuated strains of the virus effectively protects the child against measles.

Velogenic newcastle disease virus tissue tropism and pathogenesis of infection in chickens by application of in situ PCR, immunoperoxase staining and HE staining

Limited deep studies are available in the field of early stages of pathogenesis of Newcastle disease virus (NDV) infection and tissue tropism of NDV. In this study, 24 specific pathogen free (SPF) chickens of white leghorn breed were infected with Newcastle disease (ND) by intranasal administration of 10⁵ 50% EID50/0.1 mL of velogenic NDV (vNDV). A second group of 15 chickens were kept as a control group. Chickens were monitored every day to record clinical signs. Infected chickens were euthanized by cervical dislocation at successive times, namely at hours (hrs) 2, 4, 6, 12, days 1, 2, 4, and 6 post-inoculation (pi). Whereas, control group chickens were euthanized on days 0, 1, 2, 4, and 6 pi. Tissues of brain, trachea, lung, caecal tonsil, liver, kidney, spleen, heart, proventriculus, intestine, and thymus were collected, fixed in 10% buffered formalin, embedded in paraffin, and sectioned. HS staining, immunoperoxidase staining (IPS) and in situ PCR were applied. It was concluded that at hr 2 pi, virus seemed to be inclined to trachea and respiratory tract. Meanwhile, it attacked caecal tonsils, intestine and bursa of Fabricus. While primary viraemia was ongoing, virus created footing in kidney and thymus. At hr 4 pi, proventriculus, liver, and spleen were attacked. However, at hr 6 pi, brain and heart were involved. Secondary viraemia probably started as early as hr 12 pi since all collected tissues were positive. Tissue tropism was determined in trachea, caecal tonsil, liver, bursa of Fabricius, intestine, proventriculus, lung, spleen, thymus, kidney, heart, and brain.

Infectious bursal disease virus tissue tropism and pathogenesis of the infection in chickens by application of in situ PCR, immunoperoxase and HE staining

Infectious bursal disease is one of an OIE list of notifiable diseases. Chicken is the only host that manifests clinical signs and its pathogenicity is correlated with the distribution of antigens in organs. This study was conducted to determine disease pathogenesis and virus tissue tropism by in situ PCR, immunoperoxidase staining (IPS), and HE staining. Twenty four chickens were infected with very virulent Infectious Bursal Disease Virus (vvIBDV). Fifteen chickens were kept as a control group. Infected chickens were sacrificed at hrs 2, 4, 6, 12, days 1, 2, 4, and 6 post-inoculation (pi). While, control chickens were euthanized on days 0, 1, 2, 4, and 6 pi. Different tissues were collected, fixed in 10% buffered formalin, and processed. At hr 2 pi, virus was detected in intestinal, junction of the proventriculus and gizzard, cecal tonsil, liver, kidney, and bursa of Fabricius. At hr 4 pi, virus reached spleen, and at hr 6 pi, it entered thymus. At hr 12 pi, virus concentration increased in positive tissues. The latest invaded tissue was muscle on day 1 pi. Secondary viraemia occurred during 12–24 h pi. In situ PCR was the most sensitive technique to highlight obscure points of infection in this study.

Robust Oncolytic Virotherapy Induces Tumor Lysis Syndrome and Associated Toxicities in the MPC-11 Plasmacytoma Model

Tumor-selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here, we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation, and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days. Secondary viremia was observed but viral replication in normal host tissues was not detected. Toxicity could be mitigated by using VSVs with slowed replication kinetics, and was less marked in animals with smaller flank tumors. The MPC-11 tumor represents an interesting model to further study the complex interplay of robust intratumoral viral replication, tumor lysis, and associated toxicities in cases where tumors are highly responsive to oncolytic virotherapy.

ID: 76: The MCMV protein M35 is a novel negative regulator of the type I IFN response

The early detection of herpesvirus infection by pattern recognition receptors (PRRs) triggers the production of type I interferons (IFN), which exert potent antiviral effects. Whilst MCMV is recognized to induce strong innate immune responses, UV inactivation of MCMV results in an enhanced type I IFN response, indicating that the virus actively downmodulates innate immune signaling. Using an unbiased luciferase-based assay to screen an MCMV cDNA library, we have identified the M35 protein as a negative regulator of PRR-dependent type I IFN signaling. Infection of primary bone marrow derived macrophages with an MCMV mutant lacking M35 (M35stop) results in increased secretion of type I IFN as compared to wild-type (WT) MCMV. To confirm the physiological role of M35, we infected BALB/c mice with MCMV M35stop to assess the subsequent type I IFN response. MCMV M35stop induces significantly higher type I IFN serum levels than WT MCMV 8 h post infection, which correlates well with expression of tegument M35 protein. MCMV M35stop replicates to significantly reduced titres compared to WT MCMV in the spleen at day 3 post infection. MCMV is then disseminated via secondary viremia to the salivary glands, a site of persistence and dissemination for MCMV. MCMV M35stop is undetectable from the salivary glands from as early as 7 days post infection. This exclusion of M35stop from the salivary glands indicates that M35 is a critical determinant of viral replication in vivo. Collectively, our data demonstrate the first characterisation of M35 as a novel antagonist of type I IFN signaling downstream of PRRs.

A Case of Chickenpox with Complication of Cellulites Leading to Respiratory Distress

Chickenpox is a common disease worldwide caused by the Varicella Zoster Virus (VZV) as a causative agent with a prominent contagious property causing severe itching and rash. The secondary viremia results in itching skin lesions. Forming an entrance gate, these vesicles lead to secondary infections. A 15 months old male infant, referred to the emergency ward with swollen neck and skin rash throughout the body, was admitted to the Pediatric Intensive Care Unit. Respiratory rate was 26/min, body temperature was 37oC, and pulse was 132/min. Pathological examination findings were facial edema and edematous neck and diffuse rash. No abnormal laboratory findings other than anemia and elevated CRP were found. The patient was diagnosed with secondary bacterial infection – cellulite. The respiratory distress was associated with the edema resulting from the infection. We presented the case of cellulite that was advanced to an extent to cause respiratory problems following the itchy vesicle. Measures to be taken for children as the carriers of the disease can be listed as local antiseptic applications, antihistaminic to prevent itching and avoidance of non-steroidal anti-inflammatory (NSAI) administration. We wanted to remind that taking simple measures could reduce the secondary bacterial complications of the commonly encountered disease.

Endothelial Cells and CMV Dissemination

Using the murine CMV animal model and the well-established model of Cre-lox-P-mediated green-fluorescence tagging of endothelial cell (EC)-derived mouse CMV to quantify the role of infected ECs in transplantation-associated CMV dissemination (in mice expressing Cre recombinase under the control of either the Tie2 or the Tek promoter selectively expressed in vascular EC-Tie-Cre and Tek-Cre mice), it was shown that EC-derived virus contributed to 50% of the total viral load during primary infection, and there was no preference for dissemination of EC-derived viruses over viruses produced by other cell types. In addition, during secondary viremia, there was only a negligible contribution of EC-derived virus to dissemination to other organs. These results are novel in the methodology employed and are somewhat interesting. However, the data are limited to the mouse model with a short-term follow-up, and the immunodeficient host has not yet been studied. In humans, these conclusions must be taken with caution. First, in primary infection occurring through natural routes, epithelial cells are infected first, then ECs, unless primary infection occurs through blood transfusion, in which case endothelial vascular cells may become infected first. In both cases, the virus transport occurs through the intervention of leukocytes, namely monocytes and polymorphonuclear leukocytes. As monocytes differentiate to macrophages, they become highly susceptible to human CMV replication inside organ tissues, while polymorphonuclear leukocytes are active in virus capturing from infected endothelial vascular cells and transporting to distant sites.

Shedding Light on the Elusive Role of Endothelial Cells in Cytomegalovirus Dissemination

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre + heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre + transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre + recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.

Immunological and Viral Determinants of Dengue Severity in Hospitalized Adults in Ha Noi, Viet Nam

BackgroundThe relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi.Methods and Findings158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn't find an association between plasma viral RNA concentration and clinical severity.ConclusionDengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.

AN EXPERIMENTAL STUDY ON EARLY PATHOGENESIS OF A VERY VIRULENT ISOLATE OF INFECTIOUS BURSAL DISEASE VIRUS, EMPLOYING IMMUNOHISTOCHEMISTRY

Summary In this study, immunohistochemistry was used to clarify the early stages of viral kinetics and cyclic course of IBDV, IR499, which has been described earlier as a very virulent strain (vvIBDV). Fifteen, 4week-old SPF chickens were inoculated with 10³ EID50 of vvIBDV, IR499, via oculo/nasal route. Five birds served as controls, and inoculated with phosphate buffered saline (PBS). The birds were then bled, and tissue samples from bursa of Fabricius, cecal tonsils, liver, spleen, thymus and thigh muscle were harvested at 3, 6, 12, 24 and 48 h post-inoculation (p.i.). Typical positive signals were first observed as early as 3 h p.i. in lymphoid cells of cecal tonsils (the organ of primary affinity) and Kupfer cells of liver. Viral antigens in bursa were first found at 6 h p.i. which represents the occurrence of primary viraemia. After secondary viraemia, the virus appeared in spleen and thymus at 12 h p.i. These findings at early stages of viral infection, represented IBDV, IR499, as a very virulent strain with a rapid and generalized course, at in vivo level.

ST-246 Antiviral Efficacy in a Nonhuman Primate Monkeypox Model: Determination of the Minimal Effective Dose and Human Dose Justification

Therapeutics for the treatment of pathogenic orthopoxvirus infections are being sought. In the absence of patients with disease, animal models of orthopoxvirus disease are essential for evaluation of the efficacies of antiviral drugs and establishment of the appropriate dose and duration of human therapy. Infection of nonhuman primates (NHP) by the intravenous injection of monkeypox virus has been used to evaluate a promising therapeutic drug candidate, ST-246. ST-246 administered at 3 days postinfection (which corresponds to the secondary viremia stage of disease) at four different doses (from 100 mg/kg of body weight down to 3 mg/kg) once a day for 14 days was able to offer NHP 100% protection from a lethal infection with monkeypox virus and reduce the viral load and lesion formation. In NHP, the administration of ST-246 at a dose of 10 mg/kg/day for 14 days resulted in levels of blood exposure comparable to the levels attained in humans administered 400 mg in the fed state. These results suggest that administration of an oral dosage of 400 mg once daily for 14 days will be effective for the prevention or treatment of smallpox or monkeypox infections in humans.

Real-time PCR investigation of feline leukemia virus proviral and viral RNA loads in leukocyte subsets

Cats exposed to feline leukemia virus (FeLV), a naturally occurring gammaretrovirus develop either progressive or regressive infection. Recent studies using analyses with enhanced sensitivity have correlated loads throughout FeLV with the clinical outcome, though remarkably, during the acute phase of infection, proviral and viral RNA burdens in the peripheral blood do not differ between groups. We hypothesized that viral loads in specific leukocyte subsets influence the infection outcome. Using a method established to determine the proviral and cell-associated viral RNA loads in specific leukocyte subsets, we evaluated viral loads in eleven FeLV-exposed specific pathogen-free (SPF) cats 2.5 years post-infection. Six cats had undergone regressive infection whereas five were persistently viremic. Aviremic cats had lower total proviral blood loads than the persistently infected cats and FeLV proviral DNA was shown to be integrated into genomic DNA in four out of four animals. Lymphocytes were predominantly infected vs. moncytes and granulocytes in aviremic cats. In contrast, persistently viremic cats were provirus-positive in all leukocyte subsets. The acute phase kinetics of FeLV infection were analyzed in two additional cats; an early lymphoreticular phase with productive infection in lymphocytes in both cats and in monocytes in one cat was followed by infection of the granulocytes; both cats became persistently infected. These results indicate that FeLV persistent viremia is associated with secondary viremia of bone marrow origin, whereas regressive cats only sustain a non-productive infection in low numbers of lymphocytes.

Antibody‐Dependent Cellular Cytotoxicity Mediated by Plasma Obtained before Secondary Dengue Virus Infections: Potential Involvement in Early Control of Viral Replication

Preexisting dengue virus (DV)-specific antibodies from prior heterologous DV infection may have several effects in secondary DV infection. These antibodies may mediate protective effects by means of antibody-dependent cellular cytotoxicity (ADCC), in which virus-specific antibodies bind to the surface of heterologous DV-infected cells and mediate natural killer cell lysis. In the present study, we examined the ability of plasma obtained before secondary DV infection to induce ADCC of DV-infected cells. Plasma samples were obtained before DV2 or DV3 infection in a prospective cohort study of Thai schoolchildren. The ADCC activity in the plasma samples was measured by (51)Cr-release assay, using persistently DV2- or DV3-infected Raji cells as targets. ADCC activity in plasma obtained before secondary infection directly correlated with neutralizing antibody titers, anti-DV immunoglobulin G1 levels, and a multitypic 50% plaque reduction neutralization test pattern. ADCC activity in pre-secondary DV3 infection plasma samples inversely correlated with plasma viremia levels, but no such correlation was seen in pre-secondary DV2 infection plasma samples. ADCC activity did not correlate with disease severity in subsequent secondary DV2 or DV3 infection but was lowest in plasma from patients with dengue hemorrhagic fever due to secondary DV3 infection. ADCC may contribute to the early control of secondary DV3 viremia in vivo.

The Cause of Death in Smallpox: An Examination of the Pathology Record

Because the cause of death in smallpox remains controversial, the human pathology record was examined. The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed. The skin lesions in smallpox developed as a result of viral damage and inflammation. Secondary bacterial infection did not occur until the scabs started shedding. During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency. The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis. The cytopathic effects of smallpox cause death. The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition. In a future outbreak, antibiotic therapy would minimally influence mortality.

Apoptosis during ectromelia orthopoxvirus infection is DEVDase dependent: in vitro and in vivo studies

Ectromelia virus (EV), which causes mousepox, is a member of the orthopoxviruses that are defined as being able to suppress apoptosis. Caspase-3 is one of the key effector proteases which regulates the apoptotic cascade and which is responsible for DNA fragmentation observed during apoptosis. It is well known that viruses, especially poxviruses, can inhibit caspase activity. Here, we report that EV can regulate apoptosis in vitro, suppressing the activity of caspases recognizing the DEVD (Asp–Glu–Val–Asp) motif (caspase-3 and -7) before successful virus replication is completed. Caspase-3 activity measurement showed that an increase in caspase-3 activity preceded the peak of DNA fragmentation demonstrated by TUNEL staining of L929 and RK-13 cells. By using specific caspase inhibitors (Ac-DEVD–CHO, Ac-IETD–CHO and zVAD–fmk), we showed that caspase-3 and -7 (DEVDases) are major effector caspases during EV-induced apoptosis in permissive L929 and RK-13 cell cultures. Apoptosis in vivo seems to play an important role during viraemia as well as during the clearance of EV from genetically susceptible BALB/c (H-2 d) mice. However, as shown by measurement of caspase-3 activity, caspase-3 protein detection and M30-antibody staining, both DEVDases seem to play an important role during EV clearance from draining lymph nodes and conjunctivae at 15 days p.i. up to 20 days p.i., whereas in the liver and spleen DNA fragmentation coexisted with viral multiplication and secondary viraemia. Apoptosis was DEVDase dependent only in the liver, while spleen DNA fragmentation observed between 5 and 10 days p.i. was caspase independent. Therefore, we conclude that DEVDase- (caspase-3- and caspase-7-) dependent apoptosis is an important mechanism regulating the resolution of EV infection.

Pathogenesis and immune response in Atlantic salmon (Salmo salar L.) parr experimentally infected with salmon pancreas disease virus (SPDV)

Atlantic salmon parr were injected intraperitoneally with salmon pancreas disease virus (SPDV) grown on CHSE-214 cells. The viraemia, the histopathological changes in target organs and some immune parameters were taken at intervals up to 30 days post-infection (dpi). The earliest kind of lesion was necrosis of exocrine pancreas, appearing as soon as 2dpi. It progressed towards complete tissue breakdown at 9dpi before resolving gradually. Concurrent to this necrosis, a strong inflammatory response was in evidence from 9dpi in the pancreatic area for a majority of fish. A necrosis of the myocardial cells of the ventricle occurred in infected fish mainly at 16dpi and it faded thereafter. The monitoring of the plasma viral load showed a rapid haematogenous spreading of SPDV, peaking at 4dpi, but also the absence of a secondary viraemia. No interferon (IFN) was detected following the infection of parr with SPDV, probably owing to an IFN activity in Atlantic salmon below the detection level of the technique. Neutralising antibodies against SPDV were in evidence from 16dpi and they showed a time-related increasing titre and prevalence. The phagocytic activity in head-kidney leucocytes was always significantly higher in the infected fish than in the control fish, being particularly high by 9dpi. Lysozyme and complement levels were both increased and they peaked significantly in the infected fish at 9 and 16dpi respectively. These results demonstrated that an experimental infection of Atlantic salmon parr with SPDV provoked a stimulation of both specific and non-specific immunity with regards to the viraemia and the histopathology.

Viral encephalitis.

Viral encephalitis.