Frequent detection of HIV-1-specific mRNAs in infected individuals suggests ongoing active viral expression in all stages of disease.
It has been shown that only a small fraction of CD4+ T cells are infected with human immunodeficiency virus type 1 (HIV-1) in vivo, particularly early in the course of infection. An even smaller proportion of cells have been shown to be expressing virus. Recent studies suggest that plasma viremia in asymptomatic HIV-infected individuals, representing active viral replication, is more common than was previously believed (range 23-100% of patients). To determine the in vivo state of HIV expression, samples of peripheral blood of 49 HIV-infected individuals at all stages of disease were examined. All subjects were positive for viral DNA by standard polymerase chain reaction (PCR), and a modified PCR was utilized to detect HIV-specific mRNAs (gag, major splice junction, env, and tat/rev). Patient's plasma was also assayed for p24 antigen and viremia. The results were as follows: (formula: see text) Overall, the findings suggest that active viral expression occurs at all stages of HIV infection. In particular, the presence of gag mRNA was determined in only 2 of 14 patients with T4% greater than 30% but in 20 of 35 patients with T4% less than or equal to 30% (p less than 0.05), demonstrating a direct association between the presence of message for a structural protein, and more advanced immunosuppression. Determination of the expression of certain HIV-specific messages from within a patient's cells adds a new dimension to understanding the pathogenesis of HIV infection. The presence of HIV-specific mRNAs, and in particular gag message, in many healthy seropositives may further argue for early initiation of antiviral therapy.
Schnittman
S M
SM
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Greenhouse
J J
JJ
Lane
H C
HC
Pierce
P F
PF
Fauci
A S
AS
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000097:blood; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007958:Leukocyte Count; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014758:Viral Core Proteins / Q000097:blood; D014766:Viremia / Q000235:genetics*; D014779:Virus Replication
D004279:DNA, Viral; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D012333:RNA, Messenger; D014758:Viral Core Proteins