7 P De Togn e t a / , i b~d , p 703, T. A Banks et a1 , J /n?n?uno/ 155, 1685 (1 995) 8 Mce were ~mmun~zed intrapertoneally w~th 100 &I of phosphate-buffered sane contanng 10% SRBCs (22) Ten days later, spleens were harvested, embedded In 0 C.T compound (M~les), and frozen In q u d ntrogen Frozen t~ssue sections (6 to 10 &m th~ck) were f~xed n cold acetone Endogenous per-ox~dase was q~~enched w~th 0 2% H, O, n methanol Sectons were sta~ned by f~rst ncubatng w~t h PNA-b~o t~n (Vector) and w~th rat antserum produced to IgD (Southern B~otechnology) After wash~ng, the sections were further incubated w~th strepta\/id~n conj~lgated w~th alkalne phosphatase (AP) (Zymed) and rabb~t ant~body to rat IgG conjugated w~th horse-rad~sh perox~dase (HRP) (Southern B~otechnology) Color development for bound AP and HRP was w~th an AP reacton k~t (Vector) and w~t h d~arn~nobenz-d~ne Sect~ons were then countersta~ned w~th 1 % methyl green 9 M. L Rose, M S C B~rbeck, V J Wall~s, J A Forrester. A J Daves. Nature 284, 364 (1980) 10 T
This report describes serologic evidence for a virus similar to that known as simian T-lymphotropic virus type III of African Green monkeys (STLV-IIIAGM) infecting apparently healthy people in Senegal, West Africa, and the isolation of virus from these individuals. Serum samples from selected healthy West African people showed unusual serologic profiles when tested with antigens of HTLV-III/LAV, the etiologic agent of AIDS, and of STLV-IIIAGM. The samples reacted strongly with all of the major viral antigens of STLV-IIIAGM but showed variable or no reactivity with the major viral antigens of HTLV-III/LAV by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A new human T-lymphotropic virus (HTLV-IV) isolated from these people was grown in vitro and shown to have retroviral type particles, growth characteristics, and major viral proteins similar to those of the STLV-III and HTLV-III/LAV group of retroviruses. The gp120/160, gp32, p64, p55, p53, p24, and p15 proteins precipitated were the same size as and reactive with STLV-IIIAGM proteins. The serologic data suggest that this virus shares more common epitopes with STLV-IIIAGM than with the prototype HTLV-III/LAV that infects people in the United States and Europe. Further study of this virus and of the origin of the HTLV-III/LAV group of viruses may expand our understanding of the human AIDS virus.
Virus-specific cytotoxic T lymphocytes (CTL) play a crucial role in modulating an immune response against human immunodeficiency type 1 (HIV-1) infection. The generation of effector cytotoxic cells from CTL precursors involves intricate interactions with antigen via T cell receptors (TcR) and soluble cytokines. Interleukin (IL)-7 can affect T cell maturation and differentiation. Here we report on a group of five HIV-1-positive individuals who tested negative for env- and gag-specific CTL activity. When exogenous recombinant human IL-7 was added as a stimulus to the cultures, none (0/5) of the CTL-negative individuals exhibited a CTL response. Individuals that were negative for HIV-1-specific CTL activity were found to lack IL-7 receptor (IL-7R) on CD8+ cells with a comparable reduction on CD4+ cells. Increased shedding of IL-7R in the culture supernatant was observed. A significant reduction in receptor number was detected by binding of 125I-labeled IL-7 and Scatchard analysis. The lack of IL-7R is probably not due to endogenous IL-7, since it was not detectable in the culture supernatants of the patients studied. HIV-1 proteins may cause down-modulation of IL-7R expression, either by producing an insufficient number of molecules or by rapid decay of IL-7R on T cells. These changes may alter the cells' capability to respond to the IL-7 growth signal, resulting in CTL failure and subsequent mishandling of the virus.
In-frame stop codons were introduced into the coding region of human immunodeficiency virus type 1 (HIV-1) transmembrane protein (gp4l). Truncation of 147 amino acids from the carboxyl terminus of gp4l (TM709) significantly decreased the stability and cell surface expression of the viral Env proteins, while truncation of 104 amino acids (TM752) did not. Truncation of 43 or more amino acids from the carboxyl terminus of gp4l generated mutant viruses which were noninfectious in several human CD4+ T lymphoid cell lines and fresh peripheral blood mononuclear cells. Analysis of the noninfectious mutant virions revealed 213
Specific antibodies to cell membrane antigens found on human T-cell leukemia virus (HTLV)-infected cells have been detected in Japanese patients with adult T-cell leukemia/lymphoma and in asymptomatic carriers, using a live cell-membrane immunofluorescence assay. Reactivity of the positive antisera was analyzed using radioimmunoprecipitation and NaDodSO4/PAGE with the HTLV-infected tumor cell line Hut 102 (clone B2). The major cell-associated antigens identified include two glycoproteins of -61 and 45 kDa, which appear to be the most immunogenic species in exposed people, a nonglycosylated species of 42 kDa, and four additional species that contain gag gene-encoded antigens with sizes ranging from 19 to 55 kDa. The two glycoproteins (gp6l and gp45) are encoded, at least in part, by the env gene of HTLV as evidenced by amino acid sequence analysis.
We studied the clinical status and certain hematologic and immunologic parameters in healthy prostitutes from Dakar, Senegal who were seropositive for antibodies to human immunodeficiency virus type-2 (HIV-2). Generalized lymphadenopathy and clinical signs or symptoms similar to those which are seen with human immunodeficiency virus type-1 (HIV-1) infection were not present. Comparison to seronegative prostitutes and minor surgery control patients were made and significant elevations were seen in T8 lymphocytes (p = .03), IgG (p = .0001), and beta 2-microglobulin (p = .03). The mean T4 lymphocyte count in seropositive prostitutes was lower than in seronegative prostitutes (757 vs. 1179, p = .15), but this difference was not statistically significant and appeared to be correlated with age. No significant differences were noted between the seronegative and seropositive prostitutes in lymphocyte stimulation studies to certain mitogens. Antilymphocyte antibodies above background were not present in either population. We conclude that HIV-2 is a sexually transmitted agent that produces immunologic alterations consistent with a persistent viral infection. HIV-2 seropositive prostitutes studied to date do not show clinical signs of immune suppression, as has been described with HIV-1 infection. The pathogenic potential of HIV-2 appears to differ from that of HIV-1, the etiologic agent of the AIDS pandemic.
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