An immune control model for viral replication in the CNS during presymptomatic HIV infection
M McCrossan, M Marsden, F W Carnie, S Minnis, B Hansoti, I C Anthony, R P Brettle, J E Bell, P Simmonds
Deanery of Clinical Sciences
Deanery of Molecular, Genetic and Population Health Sciences
The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P <0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P <0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.
Pt 2
https://doi.org/10.1093/brain/awh695
CD8-Positive T-Lymphocytes
DNA, Viral
HIV Envelope Protein gp120
HIV Infections
HIV-1
Lymphoid Tissue
Models, Immunological
Proviruses
Sequence Analysis, DNA
Virus Replication
10.1093/brain/awh695
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HIV Infections Medicine & Life Sciences 100%
Lymphocytes Medicine & Life Sciences 23%
Lymphoid Tissue Medicine & Life Sciences 12%
Infections Medicine & Life Sciences 10%
Immunosuppression Medicine & Life Sciences 10%
McCrossan, M., Marsden, M., Carnie, F. W., Minnis, S., Hansoti, B., Anthony, I. C., Brettle, R. P., Bell, J. E., & Simmonds, P. (2006). An immune control model for viral replication in the CNS during presymptomatic HIV infection. Brain, 129(Pt 2), 503-16. https://doi.org/10.1093/brain/awh695
McCrossan, M ; Marsden, M ; Carnie, F W et al. / An immune control model for viral replication in the CNS during presymptomatic HIV infection. In: Brain. 2006 ; Vol. 129, No. Pt 2. pp. 503-16.
@article{edd7c918a80342a58ccdd037257972ba,
title = "An immune control model for viral replication in the CNS during presymptomatic HIV infection",
abstract = "The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P <0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P <0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.",
keywords = "Adult, Amino Acid Sequence, Base Sequence, CD8-Positive T-Lymphocytes, Central Nervous System, DNA, Viral, Female, HIV Envelope Protein gp120, HIV Infections, HIV-1, Humans, Immunohistochemistry, Lymphoid Tissue, Male, Models, Immunological, Molecular Sequence Data, Peptide Fragments, Polymerase Chain Reaction, Proviruses, Sequence Analysis, DNA, Virus Replication",
author = "M McCrossan and M Marsden and Carnie, {F W} and S Minnis and B Hansoti and Anthony, {I C} and Brettle, {R P} and Bell, {J E} and P Simmonds",
doi = "10.1093/brain/awh695",
number = "Pt 2",
McCrossan, M, Marsden, M, Carnie, FW, Minnis, S, Hansoti, B, Anthony, IC, Brettle, RP, Bell, JE & Simmonds, P 2006, 'An immune control model for viral replication in the CNS during presymptomatic HIV infection', Brain, vol. 129, no. Pt 2, pp. 503-16. https://doi.org/10.1093/brain/awh695
An immune control model for viral replication in the CNS during presymptomatic HIV infection. / McCrossan, M; Marsden, M; Carnie, F W et al.
In: Brain, Vol. 129, No. Pt 2, 02.2006, p. 503-16.
T1 - An immune control model for viral replication in the CNS during presymptomatic HIV infection
AU - McCrossan, M
AU - Marsden, M
AU - Carnie, F W
AU - Minnis, S
AU - Hansoti, B
AU - Anthony, I C
AU - Brettle, R P
AU - Bell, J E
AU - Simmonds, P
N2 - The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P <0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P <0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.
AB - The brain is targeted by human immunodeficiency virus type 1 (HIV-1) during the course of untreated infection, leading to cognitive impairment, neurological damage and HIV encephalitis (HIVE). To study early dynamics of HIV entry into the brain, we examined a unique autopsy series of samples obtained from 15 untreated individuals who died in the presymptomatic stages of infection from non-HIV causes. HIV was detected and quantified by limiting dilution PCR and genetically characterized in the V3 region of env. Limiting dilution was shown to be essential for correct estimation of genetic partitioning between brain- and lymphoid-associated HIV populations. While no actively expressing HIV-infected cells were detected by immunohistochemistry, variable and generally extremely low levels of proviral DNA were detected in presymptomatic brain samples. V3 region sequences were frequently genetically distinct from lymphoid-associated HIV variants, with association index (AI) values similar to those observed in cases of HIVE. Infiltration of CD8 lymphocytes in the brain was strongly associated with expression of activation markers (MHCII; R = 0.619; P <0.05), the presence of HIV-infected cells (proviral load; R = 0.608; P <0.05) and genetic segregation of brain variants from populations in lymphoid tissue (AI value, R = -0.528; P approximately 0.05). CD8 lymphocytes may thus limit replication of HIV seeded into the brain in early stages of infection. Neurological complications in AIDS occur when this control breaks down, due to systemic immunosuppression from HIV that destroys CD8 lymphocyte function and/or through the evolution of more aggressive neuropathogenic variants.
KW - Adult
KW - Amino Acid Sequence
KW - Base Sequence
KW - CD8-Positive T-Lymphocytes
KW - Central Nervous System
KW - DNA, Viral
KW - HIV Envelope Protein gp120
KW - HIV Infections
KW - HIV-1
KW - Lymphoid Tissue
KW - Male
KW - Models, Immunological
KW - Molecular Sequence Data
KW - Polymerase Chain Reaction
KW - Proviruses
KW - Sequence Analysis, DNA
KW - Virus Replication
U2 - 10.1093/brain/awh695
DO - 10.1093/brain/awh695
IS - Pt 2
McCrossan M, Marsden M, Carnie FW, Minnis S, Hansoti B, Anthony IC et al. An immune control model for viral replication in the CNS during presymptomatic HIV infection. Brain. 2006 Feb;129(Pt 2):503-16. https://doi.org/10.1093/brain/awh695