title: Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.
abstract: Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.|Seção de Virologia, Setor Análises Clínicas, Hospital de Clínicas-UFPR, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil. sergio.ma@ufpr.br.|Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: de Almeida
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.|Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil.
authors.forename: Indianara
authors.initials: I
authors.lastname: Rotta
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Clea E
authors.initials: CE
authors.lastname: Ribeiro
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Michelli F
authors.initials: MF
authors.lastname: Oliveira
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillon
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Pereira
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Cunha
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Marise
authors.initials: M
authors.lastname: Zonta
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Joao França
authors.initials: JF
authors.lastname: Bents
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Raboni
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Davey
authors.initials: D
authors.lastname: Smith
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000276:immunology / Q000821:virology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018946:Chemokine CCL5 / Q000097:blood / Q000134:cerebrospinal fluid; D018792:Encephalitis, Viral / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D004676:Myelin Basic Protein / Q000097:blood / Q000134:cerebrospinal fluid; D016900:Neurofilament Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D010802:Phylogeny; D012367:RNA, Viral / Q000134:cerebrospinal fluid*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D015483:HIV Antibodies; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D012367:RNA, Viral; C044882:neurofilament protein L
keywords: Biomarkers; CSF; Central nervous system; Compartmentalization; HIV; Neurologic manifestations; New generation sequence; Subtype; Subtype C