title: Envelope gene evolution and HIV-1 neuropathogenesis.
abstract: In the era of combined antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) account for 40 to 56% of all HIV+cases. During the acute stage of HIV-1 infection (<6 months), the virus invades and replicates within the central nervous system (CNS). Compared to peripheral tissues, the local CNS cell population expresses distinct levels of chemokine receptors, which levels exert selective pressure on the invading virus. HIV-1envelope(env) sequences recovered from the brains and cerebrospinal fluid (CSF) of neurocognitively impaired HIV+subjects often display higher nucleotide variability as compared to non-impaired HIV+subjects. Specifically,envevolution provides HIV-1 with the strategies to evade host immune response, to reduce chemokine receptor dependence, to increase co-receptor binding efficiency, and to potentiate neurotoxicity. The evolution ofenvwithin the CNS leads to changes that may result in the emergence of novel isolates with neurotoxic and neurovirulent features. However, whether specific factors of HIV-1 evolution lead to the emergence of neurovirulent and neurotropic isolates remains ill-defined. HIV-1envevolution is an ongoing phenomenon that occurs independently of neurological and neurocognitive disease severity; thus HIVenvevolution may play a pivotal and reciprocal role in the etiology of HAND. Despite the use of cART, the reactivation of latent viral reservoirs represents a clinical challenge because of the replenishment of the viral pool that may subsequently lead to persistent infection. Therefore, gaining a more complete understanding of how HIV-1envevolves over the course of the disease should be considered for the development of future therapies aimed at controlling CNS burden, diminishing persistent viremia, and eradicating viral reservoirs. Here we review the current literature on the role of HIV-1envevolution in the setting of HAND disease progression and on the impact of cART on the dynamics of viral evolution.
authors.affiliation: Department of Basic Sciences, Ponce Health Sciences University- School of Medicine / Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Fabián J
authors.initials: FJ
authors.lastname: Vázquez-Santiago
authors.affiliation: Department of Basic Sciences, Ponce Health Sciences University- School of Medicine / Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rivera-Amill
keywords: HIV; HIV-associated neurocognitive disorders; envelope; viral evolution