Fever with Positive EBV IgM Antibody Combined Multiple Subcutaneous Nodules on Lower Extremities and Cervical Lymphadenopathy Masquerading as Infectious Mononucleosis Proven as Subcutaneous Panniculitis-like T-cell Lymphoma by Subcutaneous Nodule Biopsy Consultation: a Case Report and Literature Review.

BACKGROUND: We report a case that presented as fever with positive Epstein-Barr Virus (EBV) IgM antibody combined with subcutaneous nodules on lower extremities and cervical lymphadenopathy firstly misdiagnosed as infectious mononucleosis, which was proven as subcutaneous panniculitis-like T-cell lymphoma by subcutaneous nodule biopsies. METHODS: Appropriate serum and bacteriological laboratory tests were carried out for the cause of fever. An ultrasound and subcutaneous nodule biopsies were performed. RESULTS: EBV IgM antibody was positive. An ultrasound revealed multiple subcutaneous nodules, which were prone to be lipoma on lower extremities and cervical lymphadenopathy. Subcutaneous nodule biopsies were firstly misdiagnosed as lipoma, while pathology consultation for the subcutaneous nodule biopsies diagnosed subcutaneous panniculitis-like T-cell lymphoma. CONCLUSIONS: When patients have persistent fever with positive EBV IgM antibody combined other system involvements, especially lymphadenopathy and multiple subcutaneous nodules, it should differentiate lymphoma from infectious diseases.

Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.

BACKGROUND: Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA). The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n.) or subcutaneously (s.c.) with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. CONCLUSION: Our results indicated that protection from high pathogenic H7N7 (NL/219/03) virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.

Molecular determinants of mouse neurovirulence and mosquito infection for Western equine encephalitis virus.

Western equine encephalitis virus (WEEV) is a naturally occurring recombinant virus derived from ancestral Sindbis and Eastern equine encephalitis viruses. We previously showed that infection by WEEV isolates McMillan (McM) and IMP-181 (IMP) results in high (∼90-100%) and low (0%) mortality, respectively, in outbred CD-1 mice when virus is delivered by either subcutaneous or aerosol routes. However, relatively little is known about specific virulence determinants of WEEV. We previously observed that IMP infected Culex tarsalis mosquitoes at a high rate (app. 80%) following ingestion of an infected bloodmeal but these mosquitoes were infected by McM at a much lower rate (10%). To understand the viral role in these phenotypic differences, we characterized the pathogenic phenotypes of McM/IMP chimeras. Chimeras encoding the E2 of McM on an IMP backbone (or the reciprocal) had the most significant effect on infection phenotypes in mice or mosquitoes. Furthermore, exchanging the arginine, present on IMP E2 glycoprotein at position 214, for the glutamine present at the same position on McM, ablated mouse mortality. Curiously, the reciprocal exchange did not confer mouse virulence to the IMP virus. Mosquito infectivity was also determined and significantly, one of the important loci was the same as the mouse virulence determinant identified above. Replacing either IMP E2 amino acid 181 or 214 with the corresponding McM amino acid lowered mosquito infection rates to McM-like levels. As with the mouse neurovirulence, reciprocal exchange of amino acids did not confer mosquito infectivity. The identification of WEEV E2 amino acid 214 as necessary for both IMP mosquito infectivity and McM mouse virulence indicates that they are mutually exclusive phenotypes and suggests an explanation for the lack of human or equine WEE cases even in the presence of active transmission.

Childhood Weber-Christian disease: clinical investigation and virus detection.

OBJECTIVE: To investigate clinical features of childhood Weber-Christian disease (WCD) and the relationship between WCD and virus. METHODS: The clinical characteristics, laboratory findings, therapy and clinical course of nine patients were reviewed and the viral antigens (EBV, CMV, HSV1 and HSV2) were detected. RESULTS: They were six males and three females with a median age of 9 years. They included four simple and five systemic WCD, and all presented fever and tender subcutaneous nodules. Other clinical features included hepatomegaly in nine patients, splenomegaly in two, lymphadenhypertrophy in six, respiratory system involved in two, gastrointestinal tract involved in two and convulsion and bleeding in one. Anaemia was noted in seven patients, raised ALT in three, hypergammaglobulnaemia in three, proteinuria in one and three of six patients positive of antinuclear antibodies (ANA). No viral antigens were found. Corticosteroids therapy was administrated for all patients, immunoglobulin for two, non-steroidal anti-inflammatory agents for three and cyclophosphamide for one. Five patients released after therapy and three patients died. CONCLUSIONS: WCD is a severe disease characterized by relapsing, febrile subcutaneous nodules and biopsy is needed for early diagnosis. The viral infection may not be associated with WCD.

What is your diagnosis?: Multifocal subcutaneous tumors in a young male baboon.

A juvenile male baboon (Papio cynocephalus anubis), while being held in quarantine prior to research assignment at the Washington National Primate Research Center (WaNPRC), presented with three soft tissue masses on the right elbow, wrist, and knee on routine physical examination. The masses were subcutaneous and did not appear to cause any discomfort to the animal. An excisional biopsy of the knee mass was submitted for histopathologic analysis and found to be poorly defined, rapidly growing, and of undetermined histogenesis. Euthanasia was elected, and a full necropsy done with samples collected for histopathologic analysis. By immunohistochemistry, the "large" cells in the masses were suggestive of a mesenchymal, nonmacrophage origin because of their being positive for vimentin and negative for cytokeratin and the macrophage maturation marker CD68. Eosinophilic intracytoplasmic inclusions were seen on HE-stained sections and corresponded to aggregates of ovoid to brick-shaped viral particles on transmission electron microscopy (TEM), which proved to be the key diagnostic tool for this case. The masses were determined to be Yaba monkey tumor virus (YMTV)-induced "benign histiocytomas" by TEM.