Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Dyrhol‐Riise, Anne Ma; Voltersvik, Pål; Berg, Ole G.; Olofsson, Jan; Kleivbo, Signe; Åsjö, Birgitta

doi:10.1089/088922201300119671

Cited by 10 publications

(9 citation statements)

References 53 publications

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“…Ominously, the frequency of provirus-containing resting CD4 ϩ T cells did not appear to change substantially between early and advanced HIV disease and was not influenced by effective therapy that reduced plasma viremia to undetectable levels (8,15). This finding has not yet been confirmed using a fully quantitative integration assay.…”

Section: Discussionmentioning

confidence: 90%

A Sensitive, Quantitative Assay for Human Immunodeficiency Virus Type 1 Integration

O’Doherty¹,

Swiggard

Jeyakumar³

et al. 2002

J Virol

200

241

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Quantitative methods to measure human immunodeficiency virus type 1 (HIV-1) integration promise to be important tools in dissecting the mechanisms whereby latent reservoirs of provirus are established, most notably in the resting T cells of patients receiving antiretroviral therapy. Here we describe a fluorescencemonitored, nested PCR assay that is able to quantify the relatively rare integration events that occur within these cells. Following DNA extraction, a nonkinetic preamplification step is performed with primers that bind genomic Alu elements and HIV-1 gag sequences, under conditions where primers, deoxynucleoside triphosphates, and enzyme are not limiting. This is followed by a kinetic PCR that quantitates HIV-1 long terminal repeat sequences. A T-cell-based integration standard which reflects the randomness of HIV-1 integration is also described. The assay is 10 to 100 times more sensitive than previously reported quantitative Alu PCRbased integration assays. It is specific for integration events, since no proviruses are detected in cells infected either in the presence of an integrase inhibitor or with an integrase-deficient virus. This method promises to provide important new insights into the processes underlying the accumulation and persistence of latent HIV-1 reservoirs and may eventually be useful clinically in monitoring the eradication of latent virus by novel therapies.

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Section: Discussionmentioning

confidence: 90%

A Sensitive, Quantitative Assay for Human Immunodeficiency Virus Type 1 Integration

O’Doherty¹,

Swiggard

Jeyakumar³

et al. 2002

J Virol

200

241

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“…26 A dramatic reduction was seen between 0 and 12 weeks, with a steady decline thereafter. HIV-1 RNA was still detected after 48 weeks of HAART.…”

Section: Hiv-1 P24 Antigen and Tonsillar Hiv-1 Rnamentioning

confidence: 99%

“…HIV-1 RNA was extracted from tonsillar lymphoid tissue homogenate from patients 1 through 12, as previously described, 26 and quantified by the ultrasensitive version of the Cobas Amplicor HIV-1 Monitor test. Data for HIV-1 RNA in tonsillar tissue at enrollment are presented in Table 1.…”

Section: Hiv-1 Rna Quantitation In Tonsillar Lymphoid Tissuementioning

confidence: 99%

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Cystatin A and HIV-1 p24 Antigen Expression in Tonsillar Lymphoid Follicles During HIV-1 Infection and During Highly Active Antiretroviral Therapy

Voltersvik¹,

Bostad²,

Dyrhol-Riise³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Cystatin A is a natural cysteine proteinase inhibitor and is found in a wide variety of normal cells. The physiologic role of Cystatin A is not fully known, however. Cystatin A is present in large amounts in follicular dendritic cells, which are important in HIV-1 pathogenesis. We analyzed Cystatin A expression in tonsillar sections from 20 patients at various stages of HIV-1 infection. There was a significant (P < 0.001) difference in Cystatin A fractions between patients and controls, with medians (ranges) of 0.61 (0.46-0.83) and 0.86 (0.78-0.90), respectively. Inverse correlations (Spearman rho) existed between Cystatin A and the rate of follicular fragmentation (rho = -0.658) and HIV-1 p24 antigen expression (rho = -0.622) in germinal centers and the amount of HIV-1 RNA in tonsillar tissue (rho = -0.765). The Cystatin A fraction declined from early chronic HIV-1 infection and was significantly lower in patients with a CD4 count below as compared with above 300 cells/muL of blood (P < 0.001), suggesting a favorable initiation of highly active antiretroviral therapy (HAART) at this level. Regeneration of Cystatin A to normal levels was shown in 11 patients 12 and 48 weeks after initiation of HAART, whereas the rate of follicular fragmentation was still elevated. Thus, we found Cystatin A to be a sensitive marker during HIV-1 infection and for regeneration of follicular lymphoid tissue during HAART.

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“…Serial 10-fold dilutions of DNA from each tissue were made from 1 g to 1 pg. The nested primers generated from lion TT's pol sequence were used to amplify a 133-bp sequence in a three-round nested touchdown PCR assay (15,45,57) by using the conditions described below with a Perkin-Elmer Gene Amp PCR system 9600 thermocycler.…”

Section: Animalsmentioning

confidence: 99%

Neurologic Disease in Captive Lions (Panthera leo) with Low-Titer Lion Lentivirus Infection

Brennan¹,

Podell

Wack

et al. 2006

J Clin Microbiol

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Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion, Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV displays up to 25% interclade sequence diversity, suggesting that it has been in the lion population for some time and may be significantly host adapted. Three captive lions diagnosed with LLV infection displayed lymphocyte subset alterations and progressive behavioral, locomotor, and neuroanatomic abnormalities. No evidence of infection with other potential neuropathogens was found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis consistent with lentiviral neuropathy. PCR was used to determine a partial lentiviral genomic sequence and to quantify the proviral burden in eight postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus was consistent with the LLV detected in other captive and free-ranging lions. Despite progressive neurologic signs, the proviral load in tissues, including several regions of the brain, was low; furthermore, gross and histopathologic changes in the brain were minimal. These findings suggest that the symptoms in these animals resulted from nonspecific encephalopathy, similar to human immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV) neuropathies, rather than a direct effect of active viral replication. The association of neuropathy and lymphocyte subset alterations with chronic LLV infection suggests that long-term LLV infection can have detrimental effects for the host, including death. This is similar to reports of aged sootey mangabeys dying from diseases typically associated with end-stage SIV infection and indicates areas for further research of lentiviral infections of seemingly adapted natural hosts, including mechanisms of host control and viral adaptation.Lion lentivirus (LLV; also known as feline immunodeficiency virus [FIV] of lion, Panthera leo [FIVPle]) is an FIV that is related to yet distinct from the domestic cat (Felis catus) FIV (4, 52). LLV is present in free-ranging prides at seroprevalence rates that approach 100% and is commonly detected in captive lion (Panthera leo) populations, suggesting that it is efficiently transmitted (4,19,22,25,32,42,50,52,53). Five distinct heterogeneous clades of LLV have been identified on the basis of sequence analysis of a conserved region of the pol gene. Up to 25% sequence diversity between clades has been noted in this highly conserved region of the lentiviral genome, suggesting that, for such genetic heterogeneity to occur, this virus has infected the lion population for a considerable time (4,52,53). LLV apparently causes little or no clinical disease in free-ranging lions, although clinical signs and immunopathology reminiscent of lentiviral infection have been reported in geriatric captive animals, perhaps due to their longer life spans and/or stress-related cofactors in these cohorts (6,19,22,41,42).The effects of FIV on do...

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Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Cited by 10 publications

References 53 publications

A Sensitive, Quantitative Assay for Human Immunodeficiency Virus Type 1 Integration

A Sensitive, Quantitative Assay for Human Immunodeficiency Virus Type 1 Integration

Cystatin A and HIV-1 p24 Antigen Expression in Tonsillar Lymphoid Follicles During HIV-1 Infection and During Highly Active Antiretroviral Therapy

Neurologic Disease in Captive Lions (Panthera leo) with Low-Titer Lion Lentivirus Infection

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