Virus and Virus Antigen in the Blood of Smallpox Patients Their Significance in Early Diagnosis and Prognosis

Downie, A. W.; McCarthy, K.; Macdonald, A.; MacCallum, F. O.; Macrae, A.D.

doi:10.1016/s0140-6736(53)90107-x

Cited by 37 publications

(14 citation statements)

References 4 publications

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“…Only a relatively small number of examinations were made for the presence of virus in the blood of these non-haemorrhagic smallpox patients. However, the finding of virus, even in low concentration on the 4th and 6th day of illness in two patients who recovered, is contrary to the experience of Downie et al (1953) who found no virus after the 2nd day in 25 patients who recovered. It appears that the presence of small amounts of virus in blood as late as the sixth day of illness is not incompatible with recovery.…”

Section: Neutralization Testscontrasting

confidence: 91%

Antibody response in non-haemorrhagic smallpox patients

Downie¹,

Lacoste²,

Goldstein³

et al. 1969

Epidemiol. Infect.

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The sera were collected from patients in the Infectious Diseases Hospital in Madras during the years 1963-6 and were held frozen at -200 C. until examinations were completed. There were 130 paired sera and 33 single specimens from patients taken mostly during the first 14 days of illness. In addition, there were 53 specimens collected during convalescence or after recovery. With five exceptions these 53 samples were collected between 2 and 4 weeks after the onset of illness. In all, 216 sera from 151 individuals were studied. Fourteen of the patients died, 11 of these had not been vaccinated. In all there were 21 patients who had not been vaccinated. This is a much smaller proportion of unvaccinated patients in this series than in the general population of smallpox patients in the hospital during this period (Rao, 1968). Most unvaccinated smallpox cases were in children, whereas blood for antibody studies was collected mostly from adults. Of the 151 patients studied only two were below 17 years of age: these two were unvaccinated males aged 2 and 6 years, respectively, who died of their disease.The techniques used in carrying out precipitation, HI, CFT and neutralization tests for antibody were described in the previous paper (Downie, St Vincent, Rao & Kempe, 1969). All sera were examined routinely for antigen by precipitation and complement-fixation tests using suitable dilutions of vaccinia immune rabbit serum. Blood specimens were examined for the presence of virus from 19 patients only.

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Section: Neutralization Testscontrasting

confidence: 91%

Antibody response in non-haemorrhagic smallpox patients

Downie¹,

Lacoste²,

Goldstein³

et al. 1969

Epidemiol. Infect.

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“…The T cell suppressive effect described here may explain why vaccinated monkeys are not protected from lethal MPV challenge by OPV-specific memory T cells in the absence of neutralizing antibodies (18). VAR also spreads systemically as a cellassociated viremia (20,21) and may use a similar evasion mechanism to overcome cellular immune responses of the host. Elucidation of the gene or genes in MPV that elicit this effect is an area of active investigation and will be the first step in determining whether a related homolog exists in the VAR genome.…”

Section: Discussionmentioning

confidence: 87%

“…Although MPV does not spread efficiently by human-to-human contact (12)(13)(14), it serves as an important model for smallpox (15)(16)(17)(18) and shares several key features of pathogenesis. For instance, unlike vaccinia (VV) (19), both VAR and MPV disseminate through their infected hosts mainly by a cell-associated viremia (15,(20)(21)(22)(23). Moreover, evasion of host immune responses is well documented; VAR infection of previously vaccinated humans and MPV infection of non-human primates can result in infectious virus persisting for prolonged periods of time as an asymptomatic infection in apparently healthy individuals (24)(25)(26)(27)(28)(29)(30)(31)(32).…”

mentioning

confidence: 99%

Monkeypox virus evades antiviral CD4 ⁺ and CD8 ⁺ T cell responses by suppressing cognate T cell activation

Hammarlund

Dasgupta

Pinilla

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

131

120

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Monkeypox virus (MPV) is a virulent human pathogen that has gained increased attention because of its potential use as a bioterrorism agent and inadvertent introduction into North America in 2003. The US outbreak also provided an important opportunity to study MPV-specific T cell immunity. Although MPV-specific CD4 ؉ and CD8 ؉ T cells could recognize vaccinia virus (VV)-infected monocytes and produce inflammatory cytokines such as IFN␥ and TNF␣, they were largely incapable of responding to autologous MPV-infected cells. Further analysis revealed that, unlike cowpox virus (CPV), MPV did not interfere with MHC expression or intracellular transport of MHC molecules. Instead, MPV-infected cells were capable of preventing T cell receptor (TcR)-mediated T cell activation in trans. The ability to trigger a state of nonresponsiveness represents a unique MHC-independent mechanism for blocking antiviral T cell activation and inflammatory cytokine production and is likely an important attribute involved with viral dissemination in the infected host. Although MPV does not spread efficiently by human-to-human contact (12)(13)(14), it serves as an important model for smallpox (15-18) and shares several key features of pathogenesis. For instance, unlike vaccinia (VV) (19), both VAR and MPV disseminate through their infected hosts mainly by a cell-associated viremia (15,(20)(21)(22)(23). Moreover, evasion of host immune responses is well documented; VAR infection of previously vaccinated humans and MPV infection of non-human primates can result in infectious virus persisting for prolonged periods of time as an asymptomatic infection in apparently healthy individuals (24-32).The mechanisms underlying these forms of immune evasion are not well understood. Many viruses employ a battery of immune evasion strategies (33-38) and poxviruses in particular are equipped to evade antiviral cytokines, chemokines, and/or antigen presentation (35, 39). We have shown that cowpox virus (CPV) interferes with intracellular transport of MHC class I, a process that correlated with evasion of antiviral CD8 ϩ T cell responses by CPV (40). It was recently demonstrated that CPV open reading frame 203 retains MHC class I in the ER (41), and, because MPV encodes a close homologue of CPV203, we expected to find a similar mechanism of immune evasion by MPV. In contrast, we observed that MPV did not down-regulate MHC class I, but instead used a mechanism of evasion that inhibited CD4 ϩ and CD8 ϩ T cell activation after cognate interactions with MPV-infected cells. This mechanism of abrogating local T cell responses may avoid systemic immune suppression, while at the same time protecting the viral reservoir from immune surveillance. Identification of the factor or factors involved with MPV-induced T cell inhibition could prove useful for developing new biologics aimed at preventing or alleviating T cell-mediated diseases (42, 43). Results Antiviral CD4 ؉ and CD8 ؉ T Cells Recognize VV-Infected Monocytes butNot MPV-Infected Monocytes. Several human HLA-bindi...

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“…However, the involvement of virus induced immune modulation and immune pathogenesis ("cytokine storm") were suggested to contribute to disease severity, relying on data from animal models for poxvirus infections. [8][9][10] The zoonotic disease monkeypox is considered as the most important poxvirus infection in humans since the eradication of smallpox. It is caused by MPXV, a natural pathogen of African rodents being discussed as potential agent of bioterrorism.…”

Section: The Different Generations Of Vaccinesmentioning

confidence: 99%

Smallpox vaccines: New formulations and revised strategies for vaccination

Paran¹,

Sutter²

2009

Human Vaccines

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Virus and Virus Antigen in the Blood of Smallpox Patients Their Significance in Early Diagnosis and Prognosis

Cited by 37 publications

References 4 publications

Antibody response in non-haemorrhagic smallpox patients

Antibody response in non-haemorrhagic smallpox patients

Monkeypox virus evades antiviral CD4 ⁺ and CD8 ⁺ T cell responses by suppressing cognate T cell activation

Smallpox vaccines: New formulations and revised strategies for vaccination

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Virus and Virus Antigen in the Blood of Smallpox Patients Their Significance in Early Diagnosis and Prognosis

Cited by 37 publications

References 4 publications

Antibody response in non-haemorrhagic smallpox patients

Antibody response in non-haemorrhagic smallpox patients

Monkeypox virus evades antiviral CD4 + and CD8 + T cell responses by suppressing cognate T cell activation

Smallpox vaccines: New formulations and revised strategies for vaccination

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Monkeypox virus evades antiviral CD4 ⁺ and CD8 ⁺ T cell responses by suppressing cognate T cell activation