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Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5[alpha] expression in PBMC

Aamer, Hadega A ; Rajakumar, Premeela ; Nyaundi, Julia ; Murphey-Corb, Michael

Retrovirology, 2014-05, Vol.11 (1), p.39-39 [Periódico revisado por pares]

London: BioMed Central Ltd

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  • Título:
    Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5[alpha] expression in PBMC
  • Autor: Aamer, Hadega A ; Rajakumar, Premeela ; Nyaundi, Julia ; Murphey-Corb, Michael
  • Assuntos: Acquired immune deficiency syndrome ; AIDS ; Binding sites ; Complications and side effects ; Development and progression ; Disease susceptibility ; Efficiency ; Gene expression ; Genetic aspects ; Health aspects ; HIV ; HIV (Viruses) ; Human immunodeficiency virus ; Immune system ; Infections ; Macaca mulatta ; Mutation ; Regression analysis ; Risk factors ; Simian immunodeficiency virus ; Software ; Studies ; Viral infections
  • É parte de: Retrovirology, 2014-05, Vol.11 (1), p.39-39
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
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  • Descrição: Background At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5[alpha], tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFN[gamma] in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670. Results Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2-3 challenges, 5 monkeys) and poorly susceptible ([greater than or equai to]6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5[alpha] and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5[alpha] levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7-10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller. Conclusions These results suggest that constitutively expressed TRIM5[alpha] appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5[alpha] observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic infection involving the transport of virus from the mucosal compartment to the blood. Together, these observations provide a strong incentive for a more comprehensive examination of the intrinsic, variable control of constitutive expression of these genes in the sexual transmission of HIV. Keywords: APOBEC3G, TRIM5[alpha], Tetherin, SAMHD1, Schlafen 11, Mx1, Mx2, Restriction factors, SIV, Mucosa
  • Editor: London: BioMed Central Ltd
  • Idioma: Inglês

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