Role of Natural Killer Cells in Virus Infections of Mice

Welsh, Raymond M.; Biron, Christine A.; Bukowski, Jack F.; McIntyre, Kim W.; Yang, Hao

doi:10.1159/000156943

Cited by 15 publications

(17 citation statements)

References 31 publications

(55 reference statements)

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“…They have reported that (i) virus titers were unperturbed during the early stages of infection in mice depleted of NK cells by cyclophosphamide (Biron et al 1996); (ii) Beige mice (NK deficient) synthesized normal levels of virus (Roder & Duwe 1979); (iii) adoptive transfer of NK cells into 5-day-old mice with low NK cell activity did not confer LCMV resistance even though it conferred resistance to murine CMV (Bukowski et al 1985) and (iv) depletion of NK cells (using antibody to asialo-GM1) had no effect on the synthesis of LCMV-WE or LCMV-ARM in acute or persistent infections (Bukowski et al 1983, Welsh et al 1984. Although NK cells have little impact on LCMV titers, they are purported to play a role in controlling viral dissemination (Welsh et al 1984) and in modulating T cell responses during infection (Su et al 2001). NK cells produce IFNγ, which induces the expression of major histocompatibility complex class I on antigen-presenting cells, thereby stimulating CD8 + lymphocytes that play an important role in controlling LCMV infection (Oldstone 2002).…”

Section: Discussionmentioning

confidence: 99%

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Rodas

Cairo

Djavani

et al. 2009

Mem. Inst. Oswaldo Cruz

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Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE) serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs). Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK) and γδ T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3 -CD8 + or CD3 -CD16 + and not the NKT (primarily CD3 + CD56 + ) subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and γδ T cells, indicating that this is not a pathogenic event. Vγ9 T cells, representing the majority of circulating γδ T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections. Keywords: NK cells -γδ T -rhesus macaque -LCMV -hemorrhagic feverArenaviruses are rodent-borne pathogens that have occasionally been known to cause lethal diseases in human beings (Oldstone 2002, Salvato & Rodas 2005. Every year, Lassa fever and the South American hemorrhagic fever viruses account for almost half a million cases worldwide, with approximately 16% mortality (Jahrling et al. 1985, McCormick et al. 1986, Fisher-Hoch et al. 2000. Although rodents serve as a reservoir for arenaviruses, studies of hemorrhagic fever have relied on guinea pig, hamster and primate models rather than mouse models because the disease mechanism is fundamentally different in non-reservoir species (Peters et al. 1987).Numerous murine studies of viral persistence and cell-mediated immunity have involved the prototype arenavirus, lymphocytic choriomeningitis virus (LCMV) , Ahmed et al. 1984, Salvato et al. 1991. The WE strain of LCMV is hepatotropic in mice, guinea pigs and primates (Riviere et al. 1985, Zinkernagel et al. 1986, Lukashevich et al. 2002, but in contrast to murine LCMV infections, LCMV-WE infection of rhesus macaques can resemble Lassa hemorrhagic fever in human beings (Jahrling et al. 1980, Peters et al. 1987, Lukashevich et al. 2002. The Armstrong (ARM) strain of LCMV does not cause overt disease in monkeys, even after intravenous inoculation (Danes et al. 1963, Peters et al. 1987, Lukashevich et al. 2002.Several immunological studies have shown the importance of CD8 T lymphocytes in both protection and in induction of immuno-pathogenesis i...

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Section: Discussionmentioning

confidence: 99%

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Rodas

Cairo

Djavani

et al. 2009

Mem. Inst. Oswaldo Cruz

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“…This aspect is currently under investigation in our laboratory. Activation of NK cells as a consequence of virus infections has been reported before (reviewed by Welsh et al, 1984). Infection of mice with lymphocytic choriomeningitis virus (LCMV) will result in a rapid increase of NK cell activity, which is apparently related to the induction of interferons.…”

Section: Table 3 Enhancement Of Natural Killer Cell Activity In P-2 mentioning

confidence: 96%

Enhancement of natural killer cell activity by Marek's disease vaccines¹

Heller

Schat

1987

Avian Pathology

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SUMMARYVaccination against Marek's disease with herpesvirus of turkeys (HVT) has been reported to cause increased natural killer (NK) cell activity as detected in vitro against LSCC-RP9 target cells. The effect of vaccination with SB-1 (a nononcogenic chicken herpesvirus), HVT and the HVT/SB-1 combination on NK cell activation was compared in Marek's disease susceptible (P-2) and resistant (N-2) chickens. Birds were vaccinated at 7 days of age and NK cell activity was measured between 3 and 42 days after vaccination. Both SB-1 and HVT caused a significant increase in NK cell-induced specific release. The increase was similar in N-2 and P-2 chickens for either HVT or SB-1, while the combined vaccine induced a significantly higher increase in N-2 compared to P-2 birds. The maximal effect of vaccination on NK cells was detected at 7 days after vaccination. In contrast with the results in young birds, vaccination of birds between 31 and 45 days of age caused either no effect or a suppression rather than an enhancement in NK cell activity.

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“…Moreover, during the course of a viral infection IFN-␥ may be produced not only by virus-activated T cells but also by virusactivated NK cells (33,34), and NK cell activation can be observed in mice infected with VSV or pretreated with poly(I:C) as evidenced by augmented ex vivo cytotoxicity (data not shown). To find out whether early virus-induced priming of mice for an augmented production of TNF-␣ was dependent on NK cells, we examined the susceptibility to LPS in mice depleted of NK cells and either preinfected with VSV or pretreated with poly(I:C) 1 day before LPS challenge.…”

Section: The Role Of Nk Cellsmentioning

confidence: 99%

Viral Infection Causes Rapid Sensitization to Lipopolysaccharide: Central Role of IFN-αβ

Nansen

Thomsen

2001

The Journal of Immunology

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LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point following infection. Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect. This hypersensitivity to LPS correlated with hyperproduction of TNF-α in vivo. The cellular and molecular mechanisms underlying this phenomenon were investigated using Ab-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-γ partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-αβR-deficient mice. Thus hyperproduction of TNF-α was completely abrogated in IFN-αβR-deficient mice, indicating that the principal mechanism underlying rapid virus-induced sensitization to LPS is an IFN-αβ-mediated priming of mice for an augmented production of TNF-α in response to LPS. This conclusion was further supported by the finding that pretreatment of mice with rIFN-αβ mimicked the effect of viral infection. In conclusion, our results reveal a previously unrecognized proinflammatory effect of IFN-αβ and point to a new pathway through which viral infection may influence the outcome of concurrent bacterial infection.

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Role of Natural Killer Cells in Virus Infections of Mice

Cited by 15 publications

References 31 publications

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Enhancement of natural killer cell activity by Marek's disease vaccines¹

Viral Infection Causes Rapid Sensitization to Lipopolysaccharide: Central Role of IFN-αβ

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Role of Natural Killer Cells in Virus Infections of Mice

Cited by 15 publications

References 31 publications

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

Enhancement of natural killer cell activity by Marek's disease vaccines1

Viral Infection Causes Rapid Sensitization to Lipopolysaccharide: Central Role of IFN-αβ

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Enhancement of natural killer cell activity by Marek's disease vaccines¹