While some individuals who become infected with herpesviruses are asymptomatic, others have moderate or severe symptoms. One factor that might explain differences in symptoms could be sequence differences (polymorphisms) in cellular proteins. We are determining if polymorphisms in cellular proteins correlate with infectivity of herpesviruses or severity of herpesvirus disease. Previously, we identified new polymorphisms in one of the three herpes simplex virus receptors in humans, and in a protein that binds to another of these receptors. Analysis of our patient population did not show a correlation with these polymorphisms and herpes simplex virus infection or degree of symptoms.? ? We are trying to identify novel or known viruses as causes of diseases of uncertain etiology. Blood and tissues from patients are being examined by sensitive PCR tests in an attempt to find new or known viruses that are responsible for the diseases. Previously, we evaluated biopsies from three patients who presented with fever and enlarged lymph nodes; some of these persons had fatigue and elevated levels of liver enzymes. Serologic tests for a variety of viruses were negative. Using PCR we amplified DNA from the lymph nodes and sequencing showed that the patients were infected with human herpesvirus 6. Subsequently, immunohistochemistry using antibody to human herpesvirus 6 identified the virus envelope glycoprotein in virus inclusion bodies in the lymph nodes. ? ? Cytomegalovirus causes congenital disease which can result in deafness and mental retardation in neonates, and can cause severe viral pneumonia and colitis in transplant recipients and sight-threatening retinitis in patients with AIDS. Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with a number of malignancies including Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkins disease, and post-transplant lymphoproliferative disease. Human CMV and EBV infect humans, but not small animals or nonhuman primates. The best models currently available for CMV and EBV are rhesus monkey CMV and EBV. The goal of this study is to develop an effective vaccine for these rhesus viruses and to use these as a model for vaccines for their human counterparts. We are using various approaches including soluble recombinant proteins, recombinant virus vectors expressing viral proteins, and replication defective viruses as vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000978-02
Application #
7592331
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2007
Total Cost
$369,884
Indirect Cost
City
State
Country
United States
Zip Code
Cohen, Jeffrey I; Mocarski, Edward S; Raab-Traub, Nancy et al. (2013) The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 31 Suppl 2:B194-6
Cecchini, Sylvain; Negrete, Alejandro; Virag, Tamas et al. (2009) Evidence of prior exposure to human bocavirus as determined by a retrospective serological study of 404 serum samples from adults in the United States. Clin Vaccine Immunol 16:597-604
Hoshino, Yo; Qin, Jing; Follmann, Dean et al. (2008) The number of herpes simplex virus-infected neurons and the number of viral genome copies per neuron correlate with the latent viral load in ganglia. Virology 372:56-63
Cohen, Jeffrey I (2008) Strategies for herpes zoster vaccination of immunocompromised patients. J Infect Dis 197 Suppl 2:S237-41