Target Cell Availability, Rather than Breast Milk Factors, Dictates Mother-to-Infant Transmission of SIV in Sooty Mangabeys and Rhesus Macaques

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Currently 2.
5 million children are infected with HIV, largely as a result of mother-to-child transmission, and there is no effective vaccine or cure. Studies of Simian Immunodeficiency Virus (SIV) infection of nonhuman primate species termed “natural hosts” have shown that mother-to-infant transmission of SIV in these animals is rare. Natural hosts are African monkey species that are naturally infected with SIV in the wild but do not develop AIDS. We sought to understand the mechanism by which natural hosts are protected from mother-to-infant transmission of SIV, aiming to translate our findings into novel strategies to prevent perinatal HIV infection. We found that natural host sooty mangabey infants have extremely low levels of target cells for SIV infection in lymphoid and gastrointestinal tissues. Direct comparison of infant sooty mangabeys and infant rhesus macaques (non-natural host species with high SIV transmission rates) confirmed that natural hosts have significantly lower levels of SIV target cells compared with non-natural hosts. Analysis of the breast milk of sooty mangabeys and rhesus macaques revealed similar levels of virus and ability to inhibit SIV infection. Our study provides evidence for target cell restriction as the main mechanism of protection from mother-to-infant SIV transmission in natural hosts.

Vyšlo v časopise: Target Cell Availability, Rather than Breast Milk Factors, Dictates Mother-to-Infant Transmission of SIV in Sooty Mangabeys and Rhesus Macaques. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003958
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003958

Souhrn

Zdroje

1. (2011) Towards the elimination of mother-to-child transmission of HIV. Report of a WHO technical consultation.

2. ChahroudiA, BosingerSE, VanderfordTH, PaiardiniM, SilvestriG (2012) Natural SIV hosts: showing AIDS the door. Science 335: 1188–1193.

3. ChahroudiA, MeekerT, LawsonB, RatcliffeS, ElseJ, et al. (2011) Mother-to-infant transmission of simian immunodeficiency virus is rare in sooty mangabeys and is associated with low viremia. J Virol 85: 5757–5763.

4. AmedeeAM, LacourN, RatterreeM (2003) Mother-to-infant transmission of SIV via breast-feeding in rhesus macaques. J Med Primatol 32: 187–193.

5. McClureHM, AndersonDC, FultzPN, AnsariAA, Jehuda-CohenT, et al. (1991) Maternal transmission of SIVsmm in rhesus macaques. J Med Primatol 20: 182–187.

6. AmedeeAM, RychertJ, LacourN, FreshL, RatterreeM (2004) Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques. Retrovirology 1: 17.

7. KlumppSA, NovembreFJ, AndersonDC, SimonMA, RinglerDJ, et al. (1993) Clinical and pathologic findings in infant rhesus macaques infected with SIVsmm by maternal transmission. J Med Primatol 22: 169–176.

8. PandreaI, OnangaR, SouquiereS, Mouinga-OndemeA, BourryO, et al. (2008) Paucity of CD4+ CCR5+ T cells may prevent transmission of simian immunodeficiency virus in natural nonhuman primate hosts by breast-feeding. J Virol 82: 5501–5509.

9. PandreaI, ParrishNF, RaehtzK, GaufinT, BarbianHJ, et al. (2012) Mucosal simian immunodeficiency virus transmission in African green monkeys: susceptibility to infection is proportional to target cell availability at mucosal sites. J Virol 86: 4158–4168.

10. PermarSR, KangHH, CarvilleA, MansfieldKG, GelmanRS, et al. (2008) Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys. J Immunol 181: 3643–3650.

11. WilksAB, PerryJR, EhlingerEP, ZahnRC, WhiteR, et al. (2011) High cell-free virus load and robust autologous humoral immune responses in breast milk of simian immunodeficiency virus-infected african green monkeys. J Virol 85: 9517–9526.

12. RousseauCM, NduatiRW, RichardsonBA, John-StewartGC, Mbori-NgachaDA, et al. (2004) Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission. J Infect Dis 190: 1880–1888.

13. RousseauCM, NduatiRW, RichardsonBA, SteeleMS, John-StewartGC, et al. (2003) Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 187: 741–747.

14. PillayK, CoutsoudisA, YorkD, KuhnL, CoovadiaHM (2000) Cell-free virus in breast milk of HIV-1-seropositive women. J Acquir Immune Defic Syndr 24: 330–336.

15. Van de PerreP, SimononA, HitimanaDG, DabisF, MsellatiP, et al. (1993) Infective and anti-infective properties of breastmilk from HIV-1-infected women. Lancet 341: 914–918.

16. KoulinskaIN, VillamorE, ChaplinB, MsamangaG, FawziW, et al. (2006) Transmission of cell-free and cell-associated HIV-1 through breast-feeding. J Acquir Immune Defic Syndr 41: 93–99.

17. SembaRD, KumwendaN, HooverDR, TahaTE, QuinnTC, et al. (1999) Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 180: 93–98.

18. WalterJ, GhoshMK, KuhnL, SemrauK, SinkalaM, et al. (2009) High concentrations of interleukin 15 in breast milk are associated with protection against postnatal HIV transmission. J Infect Dis 200: 1498–1502.

19. BosireR, GuthrieBL, Lohman-PayneB, MabukaJ, MajiwaM, et al. (2007) Longitudinal comparison of chemokines in breastmilk early postpartum among HIV-1-infected and uninfected Kenyan women. Breastfeed Med 2: 129–138.

20. FarquharC, Mbori-NgachaDA, RedmanMW, BosireRK, LohmanBL, et al. (2005) CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission. Curr HIV Res 3: 361–369.

21. Van de PerreP, RubboPA, ViljoenJ, NagotN, TylleskarT, et al. (2012) HIV-1 reservoirs in breast milk and challenges to elimination of breast-feeding transmission of HIV-1. Sci Transl Med 4: 143sr143.

22. MunchJ, RuckerE, StandkerL, AdermannK, GoffinetC, et al. (2007) Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 131: 1059–1071.

23. MunchJ, StandkerL, AdermannK, SchulzA, SchindlerM, et al. (2007) Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell 129: 263–275.

24. PaiardiniM, CervasiB, Reyes-AvilesE, MicciL, OrtizAM, et al. (2011) Low levels of SIV infection in sooty mangabey central memory CD(4)(+) T cells are associated with limited CCR5 expression. Nat Med 17: 830–836.

25. SumpterB, DunhamR, GordonS, EngramJ, HennessyM, et al. (2007) Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis. J Immunol 178: 1680–1691.

26. TaaffeJ, ChahroudiA, EngramJ, SumpterB, MeekerT, et al. (2010) A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4+ T-cell count whose magnitude is not predicted by viral load or immune activation. J Virol 84: 5476–5484.

27. KlattNR, VillingerF, BostikP, GordonSN, PereiraL, et al. (2008) Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. J Clin Invest 118: 2039–2049.

28. GordonSN, KlattNR, BosingerSE, BrenchleyJM, MilushJM, et al. (2007) Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 179: 3026–3034.

29. WangX, RasmussenT, PaharB, PooniaB, AlvarezX, et al. (2007) Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection. Blood 109: 1174–1181.

30. ElliottST, RiddickNE, FrancellaN, PaiardiniM, VanderfordTH, et al. (2012) Cloning and analysis of sooty mangabey alternative coreceptors that support simian immunodeficiency virus SIVsmm entry independently of CCR5. J Virol 86: 898–908.

31. RiddickNE, HermannEA, LoftinLM, ElliottST, WeyWC, et al. (2010) A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo. PLoS Pathog 6(8): e1001064.

32. OtsyulaMG, GettieA, SulemanM, TararaR, MohamedI, et al. (1995) Apparent lack of vertical transmission of simian immunodeficiency virus (SIV) in naturally infected African green monkeys, Cercopithecus aethiops. Ann Trop Med Parasitol 89: 573–576.

33. Phillips-ConroyJE, JollyCJ, PetrosB, AllanJS, DesrosiersRC (1994) Sexual transmission of SIVagm in wild grivet monkeys. J Med Primatol 23: 1–7.

34. WillumsenJF, FilteauSM, CoutsoudisA, UebelKE, NewellML, et al. (2000) Subclinical mastitis as a risk factor for mother-infant HIV transmission. Adv Exp Med Biol 478: 211–223.

35. LyimoMA, MosiMN, HousmanML, Zain-Ul-AbideenM, LeeFV, et al. (2012) Breast milk from Tanzanian women has divergent effects on cell-free and cell-associated HIV-1 infection in vitro. PLoS One 7: e43815.

36. PandreaI, ApetreiC, GordonS, BarbercheckJ, DufourJ, et al. (2007) Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts. Blood 109: 1069–1076.

37. BundersMJ, van der LoosCM, KlarenbeekPL, van HammeJL, BoerK, et al. (2012) Memory CD4(+)CCR5(+) T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1. Blood 120: 4383–4390.

38. RiddickNE, HermannEA, LoftinLM, ElliottST, WeyWC, et al. (2010) A novel CCR5 mutation common in sooty mangabeys reveals SIVsmm infection of CCR5-null natural hosts and efficient alternative coreceptor use in vivo. PLoS Pathog 6: e1001064.

39. DunhamR, PagliardiniP, GordonS, SumpterB, EngramJ, et al. (2006) The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus. Blood 108: 209–217.

40. LiB, Stefano-ColeK, KuhrtDM, GordonSN, ElseJG, et al. (2010) Nonpathogenic simian immunodeficiency virus infection of sooty mangabeys is not associated with high levels of autologous neutralizing antibodies. J Virol 84: 6248–6253.

41. BeerB, DennerJ, BrownCR, NorleyS, zur MegedeJ, et al. (1998) Simian immunodeficiency virus of African green monkeys is apathogenic in the newborn natural host. J Acquir Immune Defic Syndr Hum Retrovirol 18: 210–220.

42. SilvestriG, FedanovA, GermonS, KozyrN, KaiserWJ, et al. (2005) Divergent host responses during primary simian immunodeficiency virus SIVsm infection of natural sooty mangabey and nonnatural rhesus macaque hosts. J Virol 79: 4043–4054.

43. MilushJM, ReevesJD, GordonSN, ZhouD, MuthukumarA, et al. (2007) Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host. J Immunol 179: 3047–3056.

44. KlattNR, ShudoE, OrtizAM, EngramJC, PaiardiniM, et al. (2010) CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS Pathog 6: e1000747.

45. VanderfordTH, SlichterC, RogersKA, LawsonBO, ObaedeR, et al. (2012) Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Blood 119: 5750–5757.

46. BrenchleyJM, VintonC, TabbB, HaoXP, ConnickE, et al. (2012) Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections. Blood 120: 4172–4181.

47. BosingerSE, HosiawaKA, CameronMJ, PersadD, RanL, et al. (2004) Gene expression profiling of host response in models of acute HIV infection. J Immunol 173: 6858–6863.