Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection

Gega, Arjet; Kozal, Michael J.; Chiarella, Jennifer; Lee, Evelyn; Peterson, Julia; Hecht, Frederick; Liegler, Teri; John, Elizabeth St.; Simen, Birgitte B.; Price, Richard W.; Spudich, Serena

doi:10.1016/s2055-6640(20)30926-2

Cited by 13 publications

(3 citation statements)

References 23 publications

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“…HIV-1 invades the CNS within the first week(s) of infection and persists despite potent cART. 2,[24][25][26][27][28][29] HIV-1 neuroinvasion leads to inflammatory responses that result in the manifestation of HAND, but also to the establishment of the CNS as a site of persistent viral infection and HIV-1 compartmentalisation, as evidenced by the presence of distinct HIV-1 genetic sequences in the CNS compared to plasma and lymphoid tissues.…”

Section: Neuroinvasionmentioning

confidence: 99%

Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system

Calado,

Ferreira,

Pires

et al. 2024

Reviews in Medical Virology

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Since the identification of human immunodeficiency virus type 1 (HIV‐1) in 1983, many improvements have been made to control viral replication in the peripheral blood and to treat opportunistic infections. This has increased life expectancy but also the incidence of age‐related central nervous system (CNS) disorders and HIV‐associated neurodegeneration/neurocognitive impairment and depression collectively referred to as HIV‐associated neurocognitive disorders (HAND). HAND encompasses a spectrum of different clinical presentations ranging from milder forms such as asymptomatic neurocognitive impairment or mild neurocognitive disorder to a severe HIV‐associated dementia (HAD). Although control of viral replication and suppression of plasma viral load with combination antiretroviral therapy has reduced the incidence of HAD, it has not reversed milder forms of HAND. The objective of this review, is to describe the mechanisms by which HIV‐1 invades and disseminates in the CNS, a crucial event leading to HAND. The review will present the evidence that underlies the relationship between HIV infection and HAND. Additionally, recent findings explaining the role of neuroinflammation in the pathogenesis of HAND will be discussed, along with prospects for treatment and control.

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Section: Neuroinvasionmentioning

confidence: 99%

Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system

Calado,

Ferreira,

Pires

et al. 2024

Reviews in Medical Virology

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“…HIV invades the brain within approximately two weeks of infection, as demonstrated by both animal [17][18][19][20][21] and human [22,23] studies. The consequence of this neuroinvasion is two-fold, induction of inflammatory responses that culminate in the manifestation of HIV-Associated Neurocognitive Disorders (HAND) and the establishment of the brain as a reservoir for HIV.…”

Section: Hiv Neuroinvasionmentioning

confidence: 99%

HIV infection of non-classical cells in the brain

Wahl

Al‐Harthi

2023

Retrovirology

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HIV-associated neurological disorders (HAND) affect up to 50% of people living with HIV (PLWH), even in the era of combination antiretroviral therapy (cART). HIV-DNA can be detected in the cerebral spinal fluid (CSF) of approximately half of aviremic ART-suppressed PLWH and its presence is associated with poorer neurocognitive performance. HIV DNA + and HIV RNA + cells have also been observed in postmortem brain tissue of individuals with sustained cART suppression. In this review, we provide an overview of how HIV invades the brain and HIV infection of resident brain glial cells (astrocytes and microglia). We also discuss the role of resident glial cells in persistent neuroinflammation and HAND in PLWH and their potential contribution to the HIV reservoir. HIV eradication strategies that target persistently infected glia cells will likely be needed to achieve HIV cure.

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“…Генетические различия между популяциями ВИЧ-1, выделяемыми из плазмы и ликвора, присутствуют и в других генах, таких как tat, nef, pol [22][23][24]. Мутации, ассоциированные с лекарственной устойчивостью, могут встречаться в штаммах как из плазмы, так и из ликвора, причём в некоторых случаях мутации лекарственной устойчивости могут присутствовать у пациента в штаммах из ликвора и отсутствовать в штаммах из плазмы [25].…”

Section: Introductionunclassified

Phylogenetic position and genetic features of HIV-1 in CNS

Piterskiy,

Khodakov,

Mikheeva

et al. 2024

Journal of microbiology, epidemiology and immunobiology

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Background. Due to the wide coverage with antiretroviral therapy, the life expectancy of HIV infected people has significantly increased. Against the background of a decrease in mortality from HIV infection, HIV-associated neurocognitive disorders, which develop even during effective treatment, are of high importance. The overall prevalence of this pathology among HIV-infected people reaches 42.6%. The objective of the study was to research the genetic features and phylogenetic position of HIV-1 persisting in the central nervous system. Materials and methods. The clinical study group consisted of 38 patients with severe neurocognitive disorders against the background of HIV infection in stage 4B. The viral load of HIV-1 in blood plasma and cerebrospinal fluid (CSF) was measured using the "AmpliSens HIV Monitor-FRT" reagents kit. Sanger sequencing was performed using the AmpliSens HIV-Resist-Seq assay kit on an Applied Biosystems 3500 analyzer. Phylogenetic analysis of the pol gene fragments of HIV-1 strains (the site encoding the viral protease and part of the reverse transcriptase) was carried out using maximum likelihood method with the GTR+G nucleotide substitution model. Comparisons of the tertiary structure of viral proteins were performed according to three-dimensional models of the protease and p51 and p66 reverse transcriptase subunits obtained by homologous reconstruction using the SWISS-MODEL tools. Results. The viral load in the sample of patients with severe CNS lesions in blood plasma was 6.27 times higher than in CSF and amounted to 4.67 and 3.87 lg copies/ml respectively by median (p = 0,004). Phylogenetic analysis with the use of all available HIV-1 genomes from GenBank, which differed from the studied ones by less than 5% showed close genetic relations of viruses circulating in Chelyabinsk region, apart from strains circulating in Russian Federation, with viruses circulating in neighboring countries, in most abundance — from Ukraine and Kyrgyzstan, slightly less — from Belarus, Tajikistan, Kazakhstan and Armenia and also with strains from certain foreign countries: Poland and Germany. Phylogenetic analysis of 38 HIV-1 genomes revealed significant genetic distances between HIV isolates from blood plasma and CSF in 5 patients, 4 of whom were PWID, which may indicate an event of superinfection. The amount of independent amino acid substitutions in protease in isolates from blood plasma ranged from 1 to 3, in isolates from CSF — from 1 to 2. An amount of such substitutions in a fragment of reverse transcriptase in isolates from blood plasma ranged from 1 to 6, while in isolates from CSF, it ranged from 1 to 7. HIV isolates from blood plasma and CSF from 5 patients had differences in the tertiary structure of HIV-1 reverse transcriptase p51 subunit in amino acid positions 16–20 and 210–235. Isolates from 3 other patients differed in the tertiary structure only in amino acid positons 210–235. Isolates from 3 patients differed in the structure of HIV-1 RT p66 subunit in a non-nucleoside reverse transcriptase inhibitor binding pocket (NNRTI) region. Fixed differences in the tertiary structure of p51 subunit required at minimum only 1 amino acid substitution to emerge. Alterations in the tertiary structure of p66 subunit required at least 3 amino acid substitutions. Conclusion. Microevolution of HIV-1 proceeds in parallel within the same patient, in different compartments, which is reflected in the accumulation of amino acid substitutions different from another compartment in the conserved pol gene. There is a weak correlation between the viral load level in plasma and in CSF. The genetic heterogeneity of HIV strains from patients of the Chelyabinsk region indicates a high frequency of reintroduction of HIV infection in the region from other countries. Differences in the tertiary structure of HIV-1 reverse transcriptase between blood plasma and CSF isolates are regularly fixed in certain domens, which also confirms the presence of parallel HIV microevolution during virus persistence in tissues separated by the blood-brain barrier which allows a better understanding of the fixation trends of individual amino acid substitutions during HIV-induced damage to central nervous system.

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Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection

Cited by 13 publications

References 23 publications

Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system

Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system

HIV infection of non-classical cells in the brain

Phylogenetic position and genetic features of HIV-1 in CNS

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