A Study of Inapparent Infection in Smallpox

Heiner, Gordon G.; Fatima, Nusrat; Daniel, Richard; Cole, June L.; Anthony, Ronald L.; McCrumb, Fred R.

doi:10.1093/oxfordjournals.aje.a121319

Cited by 43 publications

(18 citation statements)

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“…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).…”

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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.

144

130

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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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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.

144

130

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“…4 'The close association of exposure factors with infection is one of the most striking findings of this study'. 5 'Under conditions of effective exposure, the vast majority of contacts will become infected, regardless of their immune status'. 6 'Systematic factors other than herd immunity must be important in determining the extend of spread'.…”

Section: Resultsmentioning

confidence: 99%

Lessons from a modern review of the smallpox eradication files

2015

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“…Subclinical infection has been implicated by epidemiological studies in which increases in either complement fixation or gel precipitation antibodies were observed in populations exposed to smallpox [33,34]. These finding have implications for immunity in a population and will be discussed further below.…”

Section: )mentioning

confidence: 99%

Smallpox: Virology, Clinical Presentation, and Prevention

Goodrich

2006

Bioterrorism Preparedness

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A Study of Inapparent Infection in Smallpox

Cited by 43 publications

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

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

Lessons from a modern review of the smallpox eradication files

Smallpox: Virology, Clinical Presentation, and Prevention

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A Study of Inapparent Infection in Smallpox

Cited by 43 publications

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

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

Lessons from a modern review of the smallpox eradication files

Smallpox: Virology, Clinical Presentation, and Prevention

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

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