The CD8 T Cell Noncytotoxic Antiviral Responses

Overview

Journal Microbiol Mol Biol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 2021 May 13

PMID 33980586

Citations 14

Authors

Maelig G Morvan

Fernando C Teque

Christopher P Locher

Jay A Levy

Affiliations

Soon will be listed here.

Abstract

The CD8 T cell noncytotoxic antiviral response (CNAR) was discovered during studies of asymptomatic HIV-infected subjects more than 30 years ago. In contrast to CD8 T cell cytotoxic lymphocyte (CTL) activity, CNAR suppresses HIV replication without target cell killing. This activity has characteristics of innate immunity: it acts on all retroviruses and thus is neither epitope specific nor HLA restricted. The HIV-associated CNAR does not affect other virus families. It is mediated, at least in part, by a CD8 T cell antiviral factor (CAF) that blocks HIV transcription. A variety of assays used to measure CNAR/CAF and the effects on other retrovirus infections are described. Notably, CD8 T cell noncytotoxic antiviral responses have now been observed with other virus families but are mediated by different cytokines. Characterizing the protein structure of CAF has been challenging despite many biologic, immunologic, and molecular studies. It represents a low-abundance protein that may be identified by future next-generation sequencing approaches. Since CNAR/CAF is a natural noncytotoxic activity, it could provide promising strategies for HIV/AIDS therapy, cure, and prevention.

Citing Articles

Post-Hoc Analysis of Potential Correlates of Protection of a Recombinant SARS-CoV-2 Spike Protein Extracellular Domain Vaccine Formulated with Advax-CpG55.2-Adjuvant.

Petrovsky N Int J Mol Sci. 2024; 25(17).

PMID: 39273405 PMC: 11395249. DOI: 10.3390/ijms25179459.

Co-Infections and Superinfections between HIV-1 and Other Human Viruses at the Cellular Level.

Acchioni C, Sandini S, Acchioni M, Sgarbanti M Pathogens. 2024; 13(5).

PMID: 38787201 PMC: 11124504. DOI: 10.3390/pathogens13050349.

Deciphering the Role of Epstein-Barr Virus Latent Membrane Protein 1 in Immune Modulation: A Multifaced Signalling Perspective.

Simicic P, Batovic M, Stojanovic Markovic A, Zidovec-Lepej S Viruses. 2024; 16(4).

PMID: 38675906 PMC: 11054855. DOI: 10.3390/v16040564.

CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha.

Teque F, Wegehaupt A, Roufs E, Killian M Viruses. 2023; 15(4).

PMID: 37112874 PMC: 10144965. DOI: 10.3390/v15040894.

Identification of m6A-related lncRNAs for thyroid cancer recurrence.

Wang X, Su D, Wei Y, Liu S, Gao S, Tian H Gland Surg. 2023; 12(1):39-53.

PMID: 36761480 PMC: 9906100. DOI: 10.21037/gs-22-678.

References

Paxton W, Koup R . Mechanisms of resistance to HIV infection. Springer Semin Immunopathol. 1997; 18(3):323-40. DOI: 10.1007/BF00813501. View

Mueller S, Jones C, Chen W, Kawaoka Y, Castrucci M, Heath W . The early expression of glycoprotein B from herpes simplex virus can be detected by antigen-specific CD8+ T cells. J Virol. 2003; 77(4):2445-51. PMC: 141123. DOI: 10.1128/jvi.77.4.2445-2451.2003. View

Castelli J, Deeks S, Shiboski S, Levy J . Relationship of CD8(+) T cell noncytotoxic anti-HIV response to CD4(+) T cell number in untreated asymptomatic HIV-infected individuals. Blood. 2002; 99(11):4225-7. DOI: 10.1182/blood-2001-11-0078. View

Mackewicz C, Ortega H, Levy J . CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual. J Clin Invest. 1991; 87(4):1462-6. PMC: 295198. DOI: 10.1172/JCI115153. View

Smith J, Daniel R . Human vaginal fluid contains exosomes that have an inhibitory effect on an early step of the HIV-1 life cycle. AIDS. 2016; 30(17):2611-2616. PMC: 6141010. DOI: 10.1097/QAD.0000000000001236. View

Wang X, Peng H, Tian Z . Innate lymphoid cell memory. Cell Mol Immunol. 2019; 16(5):423-429. PMC: 6474199. DOI: 10.1038/s41423-019-0212-6. View

Cheng-Mayer C, Seto D, Tateno M, Levy J . Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988; 240(4848):80-2. DOI: 10.1126/science.2832945. View

Blazek D, Teque F, Mackewicz C, Peterlin M, Levy J . The CD8+ cell non-cytotoxic antiviral response affects RNA polymerase II-mediated human immunodeficiency virus transcription in infected CD4+ cells. J Gen Virol. 2015; 97(1):220-224. PMC: 4772706. DOI: 10.1099/jgv.0.000326. View

Scala E, DOffizi G, Rosso R, Turriziani O, Ferrara R, Mazzone A . C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection. J Immunol. 1997; 158(9):4485-92. View

10.

Bleul C, Fuhlbrigge R, Casasnovas J, Aiuti A, Springer T . A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med. 1996; 184(3):1101-9. PMC: 2192798. DOI: 10.1084/jem.184.3.1101. View

11.

Killian M, Roop J, Ng S, Hecht F, Levy J . CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy. J Clin Immunol. 2009; 29(3):311-8. DOI: 10.1007/s10875-009-9275-y. View

12.

Tomaras G, Greenberg M . CD8+ T cell mediated noncytolytic inhibition of human immunodeficiency virus type I. Front Biosci. 2001; 6:D575-98. DOI: 10.2741/tomaras. View

13.

Tsakou-Ngouafo L, Paganini J, Kaufman J, Pontarotti P . Origins of the RAG Transposome and the MHC. Trends Immunol. 2020; 41(7):561-571. DOI: 10.1016/j.it.2020.05.002. View

14.

Borrow P, Evans C, Oldstone M . Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression. J Virol. 1995; 69(2):1059-70. PMC: 188677. DOI: 10.1128/JVI.69.2.1059-1070.1995. View

15.

Lu Y, Nerurkar V, Dashwood W, Woodward C, Ablan S, Shikuma C . Genotype and allele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders. Int J Infect Dis. 1999; 3(4):186-91. DOI: 10.1016/s1201-9712(99)90022-x. View

16.

Pal R, Garzino-Demo A, Markham P, Burns J, Brown M, Gallo R . Inhibition of HIV-1 infection by the beta-chemokine MDC. Science. 1997; 278(5338):695-8. DOI: 10.1126/science.278.5338.695. View

17.

Meyaard L, Kuiper H, Otto S, Wolthers K, van Lier R, Miedema F . Evidence for intact costimulation via CD28 and CD27 molecules in hyporesponsive T cells from human immunodeficiency virus-infected individuals. Eur J Immunol. 1995; 25(1):232-7. DOI: 10.1002/eji.1830250138. View

18.

Patterson S, Knight S . Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987; 68 ( Pt 4):1177-81. DOI: 10.1099/0022-1317-68-4-1177. View

19.

Moriuchi M, Moriuchi H . Class I-unrestricted noncytotoxic anti-HTLV-I activity of CD8(+) T cells. Blood. 2000; 96(5):1994-5. View

20.

Reuter M, Del Rio Estrada P, Buggert M, Petrovas C, Ferrando-Martinez S, Nguyen S . HIV-Specific CD8 T Cells Exhibit Reduced and Differentially Regulated Cytolytic Activity in Lymphoid Tissue. Cell Rep. 2017; 21(12):3458-3470. PMC: 5764192. DOI: 10.1016/j.celrep.2017.11.075. View