Evasion of cGAS and TRIM5 defines pandemic HIV

Zuliani-Alvarez, Lorena; Govasli, Morten L; Rasaiyaah, Jane; Monit, Chris; Sumner, Rebecca P.; McAlpine-Scott, Simon; Dickson, Claire F.; Faysal, K. M. Rifat; Hilditch, Laura; Miles, Richard J.; Bibollet-Ruche, Frédéric; Hahn, Beatrice H.; Böcking, Till; Pinotsis, Nikos; James, Leo C.; Jacques, D.A.; Towers, Greg J.

doi:10.1038/s41564-022-01247-0

Cited by 37 publications

(36 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with these, Lorena et al. found that the genetic reversal of two specific amino acid adaptations in the capsid of pandemic HIV-1(M) enables activation of cGAS and innate immune responses ( 181 ). These findings demonstrate an antagonistic role for HIV accessory proteins and capsids against the host’s innate immune response activation.…”

Section: Cgas-sting In Viral Infectious Diseasesmentioning

confidence: 84%

“…Besides, activated CD4 + T cells utilize cGAS to sense HIV for establishing a bioactive IFN-I response, which could be potentiated by HIV accessory protein Vpr ( 178 ). Whereas IFN-I induction is thought to be lacking in HIV-1 target cells due to effective evasion mechanisms ( 179 – 181 ). Recently, HIV-1 nonstructural protein viral infectivity factor (Vif) is reported to inhibit type I IFN production to facilitate immune evasion.…”

Section: Cgas-sting In Viral Infectious Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Function and regulation of cGAS-STING signaling in infectious diseases

Luo

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The efficacious detection of pathogens and prompt induction of innate immune signaling serve as a crucial component of immune defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have emerged as key mediators of type I interferon (IFN) and nuclear factor-κB (NF-κB) responses in health and infection diseases. Moreover, both cGAS-STING pathway and pathogens have developed delicate strategies to resist each other for their survival. The mechanistic and functional comprehension of the interplay between cGAS-STING pathway and pathogens is opening the way for the development and application of pharmacological agonists and antagonists in the treatment of infectious diseases. Here, we briefly review the current knowledge of DNA sensing through the cGAS-STING pathway, and emphatically highlight the potent undertaking of cGAS-STING signaling pathway in the host against infectious pathogenic organisms.

show abstract

Section: Cgas-sting In Viral Infectious Diseasesmentioning

confidence: 84%

Section: Cgas-sting In Viral Infectious Diseasesmentioning

confidence: 99%

Function and regulation of cGAS-STING signaling in infectious diseases

Luo

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Furthermore, HIV-1(M), a pandemic strain of HIV, contains a number of amino acid substitutions in its capsid protein and is uniquely capable of evading immune sensing by host innate immunity. Reversing the HIV-1(M) capsid mutations results in induction of type-I IFN genes and suppression of viral replication to levels comparable to non-pandemic HIV-1, suggesting that HIV-1(M) reaches pandemic levels as a consequence of adaptations in its capsid that aid type-I IFN evasion [ 45 ].…”

Section: Adaptation To Innate Interferon Signalling Can Results In Im...mentioning

confidence: 99%

On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses

Warger

Gaudieri

2022

Viruses

View full text Add to dashboard Cite

Host immunity can exert a complex array of selective pressures on a pathogen, which can drive highly mutable RNA viruses towards viral escape. The plasticity of a virus depends on its rate of mutation, as well as the balance of fitness cost and benefit of mutations, including viral adaptations to the host’s immune response. Since its emergence, SARS-CoV-2 has diversified into genetically distinct variants, which are characterised often by clusters of mutations that bolster its capacity to escape human innate and adaptive immunity. Such viral escape is well documented in the context of other pandemic RNA viruses such as the human immunodeficiency virus (HIV) and influenza virus. This review describes the selection pressures the host’s antiviral immunity exerts on SARS-CoV-2 and other RNA viruses, resulting in divergence of viral strains into more adapted forms. As RNA viruses obscure themselves from host immunity, they uncover weak points in their own armoury that can inform more comprehensive, long-lasting, and potentially cross-protective vaccine coverage.

show abstract

“…Lima et al showed that STING and cGAS gene expressions were downregulated among HIV‐infected persons after antiretroviral therapy 55 . In addition, a very recent paper demonstrated that through its capsid the pandemic HIV M strain can inhibit cGAS and TRIM5 activation, which results in silent viral replication in myeloid cells 56 . Therefore, activating HIV‐inhibited intracellular innate immunity is beneficial for infected cells as to control of HIV replication and spread.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic DNA sensor activation inhibits HIV infection of macrophages

Zhang

Liu

Zhou

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN)‐dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte‐derived macrophages (MDMs) can inhibit human immunodeficiency virus (HIV). We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication. MDMs treated with poly(dA:dT) or poly(dG:dC) expressed higher levels of both type I and type III IFNs than untreated cells. Activation of the DNA sensors in MDMs also induced the expression of the multiple intracellular anti‐HIV factors, including IFN‐stimulated genes (ISGs: ISG15, ISG56, Viperin, OAS2, GBP5, MxB, and Tetherin) and the HIV restriction microRNAs (miR‐29c, miR‐138, miR‐146a, miR‐155, miR‐198, and miR‐223). In addition, the DNA sensor activation of MDM upregulated the expression of the CC chemokines (RANTES, MIP‐1α, MIP‐1β), the ligands for HIV entry coreceptor CCR5. These observations indicate that the cytosolic DNA sensors have a protective role in the macrophage intracellular immunity against HIV and that targeting the DNA sensors has therapeutic potential for immune activation‐based anti‐HIV treatment.

show abstract

Evasion of cGAS and TRIM5 defines pandemic HIV

Cited by 37 publications

References 89 publications

Function and regulation of cGAS-STING signaling in infectious diseases

Function and regulation of cGAS-STING signaling in infectious diseases

On the Evolutionary Trajectory of SARS-CoV-2: Host Immunity as a Driver of Adaptation in RNA Viruses

Cytosolic DNA sensor activation inhibits HIV infection of macrophages

Contact Info

Product

Resources

About