Abstract
Asian macaques infected with simian immunodeficiency viruses (SIVs) isolated from African non-human primates develop a disease similar to human AIDS. SIV enters its target cells by binding to CD4 and a coreceptor, typically CCR5. Maraviroc is an entry inhibitor of human immunodeficiency virus type 1 (HIV-1) that prevents the interaction between CCR5 and the surface subunit gp120 of the viral envelope glycoprotein (Env). Thus far, the activity of maraviroc on SIV entry has been poorly studied. Here, we determined in vitro pharmacological parameters of the effect of maraviroc on the SIV Env association with CCR5. Cell-to-cell fusion inhibition assays were used to compare the susceptibility to maraviroc of the SIVsmmPBj Env-CCR5 interaction with that of HIV-1BaL Env. Analysis of dose–response curves and determination of IC50 values demonstrate that increasing concentrations of maraviroc inhibit the membrane fusion activity of SIVsmmPBj Env in a manner and to an extent similar to that of HIV-1BaL Env.
References
Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosiers RC, Tiollais P, Sonigo P (1987) Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature 328:543–547
Sharp PM, Hahn BH (2011) Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1:a006841
Evans DT, Silvestri G (2013) Nonhuman primate models in AIDS research. Curr Opin HIV AIDS 8:255–261
Clapham PR, Weiss RA (1997) Immunodeficiency viruses. Spoilt for choice of co-receptors. Nature 388:230–231
Affranchino JL, González SA (2014) Understanding the process of envelope glycoprotein incorporation into virions in simian and feline immunodeficiency viruses. Viruses 6:264–283
Checkley MA, Luttge BG, Freed EO (2011) HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol 410:582–608
Zhu P, Chertova E, Bess J Jr, Lifson JD, Arthur LO, Liu J, Taylor KA, Roux KH (2003) Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci USA 100:15812–15817
Olshevsky U, Helseth E, Furman C, Li J, Haseltine W, Sodroski J (1990) Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol 64:5701–5707
Rizzuto C, Sodroski J (2000) Fine definition of a conserved CCR5-binding region on the human immunodeficiency virus type 1 glycoprotein 120. AIDS Res Hum Retroviruses 16:741–749
Nolan KM, Jordan AP, Hoxie JA (2008) Effects of partial deletions within the human immunodeficiency virus type 1 V3 loop on coreceptor tropism and sensitivity to entry inhibitors. J Virol 82:664–673
Chen B (2019) Molecular mechanism of HIV-1 entry. Trends Microbiol 27:878–891
Veljkovic N, Vucicevic J, Tassini S, Glisic S, Veljkovic V, Radi M (2015) Preclinical discovery and development of maraviroc for the treatment of HIV. Expert Opin Drug Discov 10:671–684
Kelly KM, Beck SE, Metcalf Pate KA, Queen SE, Dorsey JL, Adams RJ, Avery LB, Hubbard W, Tarwater PM, Mankowski JL (2013) Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. AIDS 27:F21–F28
Ren Y, Li L, Wan Y, Wang W, Wang J, Chen J, Wei Q, Qin C, Xu J, Zhang X (2016) Mucosal topical microbicide candidates exert influence on the subsequent SIV infection and survival by regulating SIV-specific T-cell immune responses. J Acquir Immune Defic Syndr 71:121–129
Brocca-Cofano E, Xu C, Wetzel KS, Cottrell ML, Policicchio BB, Raehtz KD, Ma D, Dunsmore T, Haret-Richter GS, Musaitif K, Keele BF, Kashuba AD, Collman RG, Pandrea I, Apetrei C (2018) Marginal effects of systemic CCR5 blockade with maraviroc on oral simian immunodeficiency virus transmission to infant macaques. J Virol 92:e00576-e618
Dobard CW, Taylor A, Sharma S, Anderson PL, Bushman LR, Chuong D, Pau CP, Hanson D, Wang L, Garcia-Lerma JG, McGowan I, Rohan L, Heneine W (2015) Protection against rectal chimeric simian/human immunodeficiency virus transmission in macaques by rectal-specific gel formulations of maraviroc and tenofovir. J Infect Dis 212:1988–1995
Malcolm RK, Forbes CJ, Geer L, Veazey RS, Goldman L, Klasse PJ, Moore JP (2013) Pharmacokinetics and efficacy of a vaginally administered maraviroc gel in rhesus macaques. J Antimicrob Chemother 68:678–683
Veazey RS, Ketas TJ, Dufour J, Moroney-Rasmussen T, Green LC, Klasse PJ, Moore JP (2010) Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J Infect Dis 202:739–744
Dewhurst S, Embretson JE, Anderson DC, Mullins JI, Fultz PN (1990) Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14. Nature 345:636–640
Fultz PN, Zack PM (1994) Unique lentivirus-host interactions: SIVsmmPBj14 infection of macaques. Virus Res 32:205–225
Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC (1995) Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell 82:665–674
Manrique JM, Celma CCP, Affranchino JL, Hunter E, González SA (2001) Small variations in the length of the cytoplasmic domain of the simian immunodeficiency virus transmembrane protein drastically affect envelope incorporation and virus entry. AIDS Res Hum Retroviruses 17:1615–1624
Celma CCP, Paladino MG, González SA, Affranchino JL (2007) Importance of the short cytoplasmic domain of feline immunodeficiency virus transmembrane glycoprotein for fusion activity and envelope glycoprotein incorporation into virions. Virology 366:405–414
Ovejero CA, Affranchino JL, González SA (2017) Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor. PLoS ONE 12:e0177297
Rauddi ML, Mac Donald CL, Affranchino JL, González SA (2011) Mapping of the self-interaction domains in the simian immunodeficiency virus Gag polyprotein. AIDS Res Hum Retroviruses 27:303–316
Esteva MJ, Affranchino JL, González SA (2014) Lentiviral Gag assembly analyzed through the functional characterization of chimeric simian immunodeficiency viruses expressing different domains of the feline immunodeficiency virus capsid protein. PLoS ONE 9:e114299
Affranchino JL, González SA (2006) Mutations at the C-terminus of the simian immunodeficiency virus envelope glycoprotein affect gp120-gp41 stability on virions. Virology 347:217–225
González SA, Affranchino JL (2016) Processing, fusogenicity, virion incorporation and CXCR4-binding activity of a feline immunodeficiency virus envelope glycoprotein lacking the two conserved N-glycosylation sites at the C-terminus of the V3 domain. Arch Virol 161:1761–1768
Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM, Saag MS, Wu X, Shaw GM, Kappes JC (2002) Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46:1896–1905
Chen Z, Zhou P, Ho DD, Landau NR, Marx PA (1997) Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J Virol 71:2705–2714
Arthos J, Rubbert A, Rabin RL, Cicala C, Machado E, Wildt K, Hanbach M, Steenbeke TD, Swofford R, Farber JM, Fauci AS (2000) CCR5 signal transduction in macrophages by human immunodeficiency virus and simian immunodeficiency virus envelopes. J Virol 74:6418–6424
Konopka K, Düzgüneş N (2002) Expression of CD4 controls the susceptibility of THP-1 cells to infection by R5 and X4 HIV type 1 isolates. AIDS Res Hum Retroviruses 8:123–131
Tao B, Fultz PN (1995) Molecular and biological analyses of quasispecies during evolution of a virulent simian immunodeficiency virus, SIVsmmPBj14. J Virol 69:2031–2037
Visseaux B, Charpentier C, Hurtado-Nedelec M, Storto A, Antoine R, Peytavin G, Damond F, Matheron S, Brun-Vézinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2) (2012) In vitro phenotypic susceptibility of HIV-2 clinical isolates to CCR5 inhibitors. Antimicrob Agents Chemother 56:137–139
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This research was funded by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina).
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Conceptualization, JLA and SAG; methodology, JLA and SAG; validation, IG, CAO, JLA and SAG; formal analysis, IG, CAO, JLA and SAG; investigation, IG, CAO, JLA and SAG; resources, JLA and SAG; data curation, JLA and SAG; writing-original draft preparation, JLA and SAG; writing-review and editing, IG, CAO, JLA and SAG; visualization, JLA and SAG; supervision, JLA and SAG; project administration, JLA and SAG; funding acquisition, JLA and SAG.
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Giraudy, I., Ovejero, C.A., Affranchino, J.L. et al. In vitro inhibitory effect of maraviroc on the association of the simian immunodeficiency virus envelope glycoprotein with CCR5. Virus Genes 57, 106–110 (2021). https://doi.org/10.1007/s11262-020-01816-7
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DOI: https://doi.org/10.1007/s11262-020-01816-7