Differential Pathogenicity of SHIV KB9 and 89.6 Env Correlates with Bystander Apoptosis Induction in CD4+ T cells

Autor:	Tugba Mehmetoglu-Gurbuz, Anjali Joshi, Himanshu Garg
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	hiv shiv kb9 89.6 bystander apoptosis cxcr4 ccr5 apoptosis inducing potential envelope pathogenesis caspase Microbiology QR1-502
Zdroj:	Viruses, Vol 11, Iss 10, p 911 (2019)
Druh dokumentu:	article
ISSN:	1999-4915
DOI:	10.3390/v11100911
Popis:	SHIV variants KB9 and 89.6 show differential pathogenesis in primate models with KB9 causing rapid CD4 decline while 89.6 failing to induce disease. We attempted to determine whether the differential pathogenicity of KB9 versus 89.6 was a result of differential bystander apoptosis inducing potential (AIP) of the Env glycoproteins from these viruses. We find that the KB9 Env was highly potent at inducing bystander apoptosis in CD4+ target cells compared to 89.6 Env. Cell death induction by KB9 showed classical signs of apoptosis including mitochondrial depolarization, caspase activation and PARP cleavage. Inhibiting Env mediated fusion by T20 peptide inhibited KB9 mediated bystander apoptosis. KB9 and 89.6 differed in terms of co-receptor usage with 89.6 preferring CXCR4 while KB9 using both CXCR4 and CCR5 with equal efficiency. Our study suggests that higher bystander AIP of KB9 Env compared to 89.6 may be the basis for the differential pathogenesis of these viruses.
Databáze:	Directory of Open Access Journals
Externí odkaz:	https://doaj.org/article/d55d25c80f1f4a3b8a57acfe3ce43cee Zobrazit plný text záznamu View record in DOAJ Plný text ve formátu PDF Plný text ve formátu HTML
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