PMC:7463108 / 73554-75499 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7463108","sourcedb":"PMC","sourceid":"7463108","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7463108","text":"Genetic differences among HIV-1 variants have a significant impact on HIV transmission, disease progression, as well as the response to ARV therapy (see reviews, Geretti 2006; Taylor et al. 2008; Tyor et al. 2013; Tables 1 and 2). Pre-cART studies provide substantial evidence that HIV clade differences can influence HAND (Gupta et al. 2007; Sacktor et al. 2009; Boivin et al. 2010; McArthur et al. 2010; Rao et al. 2013), with HAND severity being highest for clade D and B strains, followed by C and A clades (Tyor et al. 2013). These findings are supported by preclinical studies in which clade B or clade C HIV-infected macrophages were intracranially injected into severe combined immunodeficient mice (SCID) mice. Exposure to clade B isolates induced more severe memory deficits, as well as greater astrogliosis and neuronal damage (Rao et al. 2008, 2013). In another example, the Tat dicysteine motif (CC) at positions 30 and 31, which is commonly found in clade B isolates, appears to worsen HAND (Mishra et al. 2008; Rao et al. 2013) and has been studied extensively in vitro (Ranga et al. 2004; Rao et al. 2008; Zou et al. 2011; Krishnan and Chatterjee 2015). Clade B Tat is more intrinsically cytotoxic to primary neurons in vitro than clade C Tat (Li et al. 2008; Campbell et al. 2011; Zou et al. 2011), resulting in increased proinflammatory cytokine production (e.g., IL-6 and TNF-α) (Gandhi et al. 2009) and monocyte recruitment/migration into the brain (Ranga et al. 2004; Rao et al. 2008), and increased disruption of the BBB (Gandhi et al. 2010). Similarly, the production of the inflammatory mediators prostaglandin E2 and the thromboxane A2 receptor by astrocytes is more significantly increased by clade B than clade C gp120 (Samikkannu et al. 2011). Sequence and structural alterations in gp120 have been demonstrated between clades B and C (Gnanakaran et al. 2007) and potentially contribute to these observed 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