Changes in the viral mRNA expression pattern correlate with a rapid rate of CD4+ T-cell number decline in human immunodeficiency virus type 1-infected individuals.

AUTOR(ES)

Furtado, M R

RESUMO

The rate of disease progression varies considerably among human immunodeficiency virus type 1 (HIV-1)-infected individuals. Several cross-sectional studies have shown an association between the stage of HIV-1 disease and the viral burden or the relative levels of viral gene expression. To study the extent of HIV-1 transcription and replication and its correlations with disease progression, we quantified serial, longitudinal samples of blood cells from 10 HIV-1-infected individuals with markedly different rates of CD4+ T-cell number decline following seroconversion. After normalization for the input nucleic acid content, multiply spliced viral mRNA and unspliced viral RNA were quantified by competitive reverse transcription-PCR using oligonucleotide primers which flank the major tat/rev/nef splice junction and span an internal region of the gag open reading frame, respectively. Coamplification of internal cRNA template controls was used to normalize for variation in the efficiency of reverse transcription and in vitro enzymatic amplification. Similarly, proviral DNA was also quantified by competitive PCR performed within the linear range of amplification. Viral RNA was detected in the blood cells of each individual from all time points regardless of the rate of CD4+ T-cell decline. Unspliced genomic viral RNA rapidly increased in the blood cells from HIV-1-infected individuals who had a precipitously declining CD4+ T-cell number. In contrast, both unspliced and multiply spliced viral mRNAs remained relatively stable in the blood cells from HIV-1-infected individuals who have had a relatively benign clinical course. These data demonstrate that the extent of viral transcription and replication correlates with the rate of CD4+ T-cell number decline and that quantifying intracellular viral RNA is of potential prognostic value.

Documentos Relacionados

• Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals.
• Levels of Soluble CD40 Ligand (CD154) in Serum Are Increased in Human Immunodeficiency Virus Type 1-Infected Patients and Correlate with CD4+ T-Cell Counts
• Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals.
• Rapid CD4+ T-Cell Loss Induced by Human Immunodeficiency Virus Type 1NC in Uninfected and Previously Infected Chimpanzees
• Rapid CD4+ T-Cell Loss Induced by Human Immunodeficiency Virus Type 1NC in Uninfected and Previously Infected Chimpanzees