Immune Responses to Retroviruses

Sáez‐Cirión, Asier; Manel, Nicolas

doi:10.1146/annurev-immunol-051116-052155

Cited by 39 publications

(28 citation statements)

References 221 publications

(219 reference statements)

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“…HIV-2 degrades the restriction factor SAMHD1 through its Vpx protein, leading to efficient viral DNA synthesis and innate immune activation in DCs through cGAS. In contrast, DCs neglect sensing of HIV-1 through cGAS because the virus does not degrade SAMHD1 (Sá ez-Cirió n and Manel, 2018). Depletion of SAMHD1 using HIV-2/SIVmac Vpx protein sensitizes DCs for HIV-1 infection and restores innate immune activation in response to the virus (Manel et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

Lahaye¹,

Gentili²,

Silvin³

et al. 2018

Cell

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184

195

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Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.

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Section: Introductionmentioning

confidence: 99%

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

Lahaye¹,

Gentili²,

Silvin³

et al. 2018

Cell

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184

195

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“…However, the significance of anti-Gag responses in HIV infection remains unclear, as Gag proteins are not expressed at the cell or virion surface, and should thus not be accessible to Abs. Gag-specific Abs may still be able to capture secreted Gag, broken virions, or infected cell fragments, which may in turn facilitate the uptake and presentation of Gag antigens to Gag-specific CD4+ and CD8+ T cells, which are immunodominant in EC and thought to play a key role in suppressing HIV replication [2,69].…”

Section: Association Between Memory B Cells Responses and Hiv Neutralmentioning

confidence: 99%

“…Different groups of HIV-infected individuals naturally control HIV-1 (HIV) replication in the absence of combined antiretroviral therapy (cART): elite controllers (EC), who represent fewer than 1% of HIV-infected individuals and maintain very low to undetectable viremia (generally <50 copies HIV RNA/mL); viremic controllers (VC), who show partial viral control; and post-treatment controllers, who received cART but did not resume viral replication after treatment interruption [1,2]. Importantly, these groups of patients show a very low risk of progression to AIDS and usually maintain high CD4+ T cell counts [3].…”

Section: Introductionmentioning

confidence: 99%

“…It was long thought that cytotoxic CD8+ T cells (CTL) were the unique players involved in natural HIV control. Indeed, a fraction of EC exhibit potent CTL responses against HIVinfected cells, often associated with the expression of protective HLA alleles such as HLA-B*57 and B*27 [2]. However, a growing body of evidence suggests that the humoral response, sustained by efficient CD4+ T cell help, is also a key player in HIV control.…”

Section: Introductionmentioning

confidence: 99%

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A role for antibodies in natural HIV control

Moris

Pereira

Chakrabarti

2019

Current Opinion in HIV and AIDS

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Purpose of the review Rare patients naturally control HIV replication without antiretroviral therapy. Understanding the mechanisms implicated in natural HIV control will inform the development of immunotherapies against HIV. Elite controllers (EC) are known for developing efficient antiviral T cell responses, but recent findings suggest that antibody (Ab) responses also play a significant role in HIV control. We review the key studies that uncovered a potent memory B cell response and highly functional anti-HIV Ab in EC, and explore the mechanisms that may account for the distinct properties of their humoral response. Recent findings EC maintain a large HIV-specific memory B cell pool that is sustained by efficient Tfh function. Neutralizing Ab rarely show high titers in controllers, but seem capable, at least in certain cases, of neutralizing contemporaneous viral strains. In addition, EC display a unique HIV-specific Ab profile in terms of isotype, antigen specificity, and glycosylation pattern, resulting in polyfunctional Ab effector functions that may promote infected cell lysis and prime effectors of the antiviral immune response.

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“…Nevertheless, despite the fast mutation and evolution rates of particular viruses, a mutual adaptation between the host and the infectious agents takes place, including the reduced replication and expression of viral proteins, the modulation of the host response by viral-miRNAs, as well as the emergence of innate and adaptive immunity [ 4,5,6,7,8]. In addition to these mechanisms, cytokines produced by the host as a response to viral infections induce the expression of AID/APOBEC (Activation-Induced cytidine Deaminase/Apolipoprotein B Editing Complex) family genes, which are important for antibody maturation and inhibition of viral infections through mutagenic and non-mutagenic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

APOBEC-mediated DNA alterations: a possible new mechanism of carcinogenesis in EBV-positive gastric cancer

Bobrovnitchaia

Valieris

Drummond

et al. 2018

Preprint

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Mechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in host DNA. Here we show , after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC-mutations preferentially occuring in transcriptionally-active loci. The EBV-infection and APOBEC3 mutation-signature axis was confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.

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Immune Responses to Retroviruses

Cited by 39 publications

References 221 publications

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation

A role for antibodies in natural HIV control

APOBEC-mediated DNA alterations: a possible new mechanism of carcinogenesis in EBV-positive gastric cancer

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