Inhibitory TCR Coreceptor PD-1 Is a Sensitive Indicator of Low-Level Replication of SIV and HIV-1

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bVaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (SIV) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. Derivatives of SIVmac239 and SIVmac239⌬nef were constructed in which env sequences were replaced with those of the heterologous strain E543; these were then used in vaccine/challenge experiments. When challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing immunity despite a mismatch of Env sequences, compared to 12 of 12 monkeys with apparent sterilizing immunity when challenge virus was matched in its Env sequence. However, when challenge occurred at 6 weeks, 6 of 6 SIV239⌬nef-immunized monkeys became superinfected by challenge virus mismatched in its Env sequence (SIV239/EnvE543). These results contrast markedly not only with the results of the week 22 challenge but also with the sterilizing immunity observed in 5 of 5 SIV239⌬nef-immunized rhesus monkeys challenged at 5 weeks with SIV239, i.e., with no mismatch of Env sequences. We conclude from these studies that a mismatch of Env sequences in the challenge virus can have a dramatic effect on the extent of apparent sterilizing immunity when challenge occurs relatively early, 5 to 6 weeks after the nef-deleted SIV administration. However, by 22 weeks, mismatch of Env sequences has little or no influence on the degree of protection against challenge virus. Our findings suggest that anti-Env immune responses are a key component of the protective immunity elicited by live attenuated, nef-deleted SIV.

Section: Methodsmentioning

confidence: 99%

Influence of Mismatch of Env Sequences on Vaccine Protection by Live Attenuated Simian Immunodeficiency Virus

Manrique

Piatak²,

Lauer

et al. 2013

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“…on April 30, 2019 by guest http://jvi.asm.org/ tion as well as CD4 ϩ T cell activation (25,76). In our patient cohort, the frequency of activated CD4 ϩ and CD8 ϩ PD-1 ϩ CD38 ϩ cells was very significantly increased in rectal mucosae of noncontrollers compared to controllers (P ϭ 0.002 and P ϭ 0.001) or seronegative subjects (P ϭ 0.0002 and P ϭ 0.0002) (Fig.…”

Section: Vol 85 2011 Treg In Rectal Mucosae Of Hiv Noncontrollers 1mentioning

confidence: 99%

Increased Frequency of Regulatory T Cells Accompanies Increased Immune Activation in Rectal Mucosae of HIV-Positive Noncontrollers

Shaw

Hunt

Critchfield

et al. 2011

“…PBMC isolation and polychromatic flow cytometry staining were carried out using protocols described previously for our laboratory (29,31); the antibodies used are listed in Table 1 (Fig. 1A).…”

Section: Cd56mentioning

confidence: 99%

Simian Immunodeficiency Virus Infection Induces Expansion of α4β7⁺and Cytotoxic CD56⁺NK Cells

Reeves

Evans

Gillis

et al. 2010

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Herein we demonstrate that chronic simian immunodeficiency virus (SIV) infection induces significant upregulation of the gut-homing marker ␣4␤7 on macaque NK cells, coupled with downregulation of the lymph node-trafficking marker, CCR7. Interestingly, in naïve animals, ␣4␤7 expression was associated with increased NK cell activation and, on CD16 ؉ NK cells, delineated a unique dual-function cytotoxic-CD107a ؉ /gamma interferon (IFN-␥)-secreting population. However, while SIV infection increased CD107a expression on stimulated CD56؉ NK cells, ␣4␤7 ؉ and ␣4␤7 ؊ NK cells were affected similarly. These findings suggest that SIV infection redirects NK cells away from the lymph nodes to the gut mucosae but alters NK cell function independent of trafficking repertoires.