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.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
S M
SM
Schnittman
J J
JJ
Greenhouse
H C
HC
Lane
P F
PF
Pierce
A S
AS
Fauci
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