Biomedical subjects
Publications and source records attributed to V Bolton.
The etiologic agent of the acquired immunodeficiency syndrome is human immunodeficiency virus. We report here a case of the culturing of this agent from the placenta and suggest the clinical implications.
The human immunodeficiency virus (HIV) was isolated from the blood of 192 of 410 seropositive individuals. Original isolations were made in peripheral blood mononuclear cell (PBMC) cultures, and only one-fifth of the HIV isolates could be adapted to replicate in continuous T-cell lines. Of the 192 HIV isolates, 42 had the characteristic p24 antigen marker of the acquired immunodeficiency syndrome-associated retrovirus type 2 strain of HIV (HIV ARV-2) and 150 resembled the human T-cell lymphotropic virus type III strain of HIV (HIV HTLV-III). Significantly, primary PBMC cultures from two patients yielded multiple variants. When these variants were exposed to continuous T-cell lines, only one of them continued to replicate. The remaining variants were lost and could not be reisolated following passage back into PBMC cultures. We conclude the following from these studies: PBMC cultures are more efficient at isolating HIV than continuous T-cell lines are; some patients harbor more than one genetic variant of HIV in the blood at the same time; and continuous T-cell lines are likely to yield only a portion of the HIV variants originally present in the blood.
The effect of human interferons (IFNs) (alpha, beta, and gamma) on the in vitro replication of AIDS viruses (LAV, HTLV-III, and ARV-2) in human peripheral blood lymphocytes was investigated. At the time of peak virus production, IFN-alpha preparations (leukocyte, Namalwa, alpha 1, and alpha 2) at 100 U/ml, suppressed LAV, HTLV-III, and ARV-2 replication as measured by reverse transcriptase (RT) activity by greater than 50%. This suppression was dose dependent and high dosages (500 U/ml) of IFN-alpha resulted in almost complete suppression of RT activities (77-99%). A low dose (100 U/ml) of IFN-beta suppressed all three AIDS viruses by 75%. In contrast, human IFN-gamma at a dose range from 100 U/ml to 500 U/ml had no significant effect on the production of infectious viruses. These results indicate that only IFN-alpha and -beta are effective against LAV, HTLV-III, and ARV-2 replication. A continuous supply of IFN appeared to be essential for the constant suppression of RT activity. In fact, upon termination of single IFN treatment, enhanced virus production resulted.
Thirty-seven clinical isolates of coxsackievirus (CV) serotypes B-1, B-3, B-4, and B-5 were inoculated into male SJL mice. Twelve strains resulted in minor abnormalities of glucose metabolism in one or more of six infected mice (Tables 1 and 2). Sequential infection of male SJL mice with CVB-3, CVB-4, and CVB-5 resulted in abnormal glucose metabolism in 25 percent of the mice (Fig. 1). The glucose index of the abnormal animals was similar to that produced by sequential infection with reovirus and cytomegalovirus but less than that seen with more severe beta cell tropic agents such as streptozotocin or encephalomyocarditis virus. Infection of autoimmune New Zealand (NZB X NZW) F1 male mice with CBV-3, CVB-4, and CVB-5 resulted in transient elevation of the blood glucose concentration associated with acute acinar pancreatitis (Fig. 2). In spite of recent evidence that infection with the coxsackie B viruses can result in human diabetes mellitus, the diabetogenic potential of CVB field strains appears to be limited. Diabetes mellitus may occur as a rare event, limited to genetically susceptible hosts. Autoimmune mechanisms or repeated infection with other CVB serotypes may convert minimal beta-cell destruction into clinically overt disease.
Variants of a clinical isolate of coxsackie B-4 virus that differ in interferon (IFN) sensitivity were selected from virus stock both before and after passage in mice. IFN sensitivity was a stable property on subsequent plaque selection. The IFN-sensitive variant was less virulent than its IFN-insensitive counterpart, whether from the original virus stock or from mouse passaged virus. None of these variants was diabetogenic in mice. These studies demonstrate that coxsackievirus variants of differing IFN sensitivity exist in nature and that this property can modulate virus virulence.
The B (nondiabetogenic) and D (diabetogenic) variants of encephalomyocarditis (EMC) virus were studied to further define the role of the interferon (IFN) system in murine virus-induced diabetes mellitus. The relationship between the initial multiplicity of infection with EMC-B and the IFN yield showed that cells infected with one IFN-inducing particle produce a maximum amount of IFN, whereas IFN production is suppressed in cells infected with two or more particles. The IFN yield induced by EMC-D was less than 5% of that induced by EMC-B, allowing the designation of the B and D variants as Ifp+ and Ifp-, respectively. The Ifp+ property of the virion was shown to be responsible for the greater sensitivity of EMC-B to exogenous IFN as a result of primed local IFN induction. The data indicate that different Ifp phenotypes occur in nature and are associated with the development of diabetes in mice.
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