Chemotherapy of a herpesvirus hominis infection in newborn mice

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Title Chemotherapy of a herpesvirus hominis infection in newborn mice
Publication Type dissertation
School or College School of Medicine
Department Pathology
Author Kern, Earl Ray
Contributor Overall James C. Jr.
Date 1973-08
Description Infection of the newborn mouse with the genital (type 2) strain of Herpesvirus hominis (HVH), provides an experimental infection that closely resembles a disseminated HVH infection of the human newborn infant. This experimental infection was utilized to evaluate the therapeutic effectiveness of 5-iodo-2'-deoxyuridine (IUDR), 1-B-D arabino-furanosylcytosine (Ara-C), 9-B-D arabinofuranosyladenine (Ara-A), polyriboinosinic-polyribocytidylic acid (poly I:C), and exogenous interferon. Experiments designed to evaluate the effectiveness of these compounds included: 1) the effect of therapy on mortality of HVH type 2 infected mice, 2) the effect of treatment on the pathogenesis of the infection, 3) the relative sensitivity of the virus to each drug, and 4) the levels of drug activity obtained in target organs. The pathogenesis of HVH infection in suckling mice following intranasal inoculation involves primary replication of virus in the respiratory tract, followed by a low level viremia. Target organs such as liver, spleen, and brain are subsequently seeded with virus from the blood. The olfactory and trigeminal nerves served as alternate pathways for the virus from the nasopharynx to the central nervous system (CNS). Death of the animals appeared to result primarily from encephalitis. Therapy with IUDR had no effect on final mortality or on the mean survival time, although a significant effect on the pathogenesis of the infection was observed. Virus replication in the lung was reduced and the viremia as well as subsequent involvement of liver and spleen was completely inhibited. In contrast nerve route transmission to and replication of HVH in the CNS was not affected by therapy. The lack of inhibition of viral replication in the CNS appeared to be due to inadequate levels of IUDR in brain tissue, and is the likely explanation for the therapeutic failure of IUDR in this model infection. Therapy with ara-C did not reduce final mortality, but it did significantly increase the mean survival time by one day of those animals that died. The effects of ara-C treatment on the pathogenesis of the infection were characterized by a one day delay in the appearance of HVH in blood, liver, and spleen, and a reduction of virus replication in lung and brain, which also lasted for about one day. Treatment with ara-A also failed to affect final mortality, but increased the mean survival time by two days. This was highly significant. Therapy with ara-A markedly altered the pathogenesis of HVH infection. There was a delay or a suppression for two days of virus replication in blood, lung, liver, spleen and brain. The alteration of HVH pathogenesis in target organs of animals treated with either ara-C or ara-A coorelated with the increase observed in the mean survival time. In this experimental HVH infection of newborn mice, ara-A appeared to be more effective than was ara-C. Neither of the two drugs, however, was completely effective in inhibiting viral replication in target organs, or protecting the animals from a lethal HVH infection. Treatment with poly I:C resulted in only low levels of protection, a significant increase in the mean survival time, and a marked alteration of pathogenesis of infection. Virus replication was completely inhibited in all organs tested except brain. CNS involvement was delayed, however, for two days. Administration of 3000 units/day of exogenous interferon was not effective in decreasing final mortality, or in altering the mean survival time. The failure of interferon or interferon inducers to alter the mortality of newborn mice infected with HVH appears to be primarily due to insufficient levels of interferon in the CNS.
Type Text
Publisher University of Utah
Subject Gamma Globulin; HVH Infections
Subject MESH Herpesvirus 2, Human; Pathology
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Chemotherapy of a herpesvirus hominis infection in newborn mice." Spencer S. Eccles Health Sciences Library. Print version of "Chemotherapy of a herpesvirus hominis infection in newborn mice." available at J. Willard Marriott Library Special Collection. QR6.5 1973 .K4.
Rights Management © Earl Ray Kern.
Format application/pdf
Format Medium application/pdf
Format Extent 4,298,139 bytes
Identifier undthes,5032
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Contract No. NIH 70-2133 from the Antiviral Substances Program of the National Institute of Allergy and Infectious Disease and by Grant No. AI-10217 from the National Institute of Allergy and Infectious Disease.
Master File Extent 4,298,171 bytes
ARK ark:/87278/s6s184b5
Setname ir_etd
ID 191313
Reference URL https://collections.lib.utah.edu/ark:/87278/s6s184b5
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