ABSTRACT
It has been hypothesized that protection against human immunodeficiency virus (HIV)-1 infection may result from either acquired host immunity, inheritance of a dysfunctional CCR5 HIV-1 coreceptor, or a low or attenuated virus inoculum. Thirty-seven HIV-1-uninfected persons engaging in repeated high-risk sexual activity with an HIV-1-infected partner were prospectively studied to determine the contribution of these factors in protecting against HIV-1 transmission. More than one-third (13/36) demonstrated HIV-1-specific cytotoxicity, and this activity significantly correlated with the wild type CCR5 genotype (P=.03). Only 1 subject (3%) demonstrated the homozygous CCR5 32-bp deletion (Delta32/Delta32). Median plasma HIV-1 RNA levels from 18 HIV-1-infected sex partners were not statistically different from those of matched infected control patients. These results indicate that inheritance of the Delta32 CCR5 mutation does not account for the majority of persistently HIV-1-resistant cases, and the presence of cellular immunity in these persons suggests either undetected infection or protective immunity.
Subject(s)
Acquired Immunodeficiency Syndrome/immunology , HIV Seronegativity/genetics , HIV Seronegativity/immunology , HIV-1/immunology , Receptors, CCR5/genetics , T-Lymphocytes/immunology , Adult , Female , HIV Antigens/immunology , Heterosexuality , Homosexuality, Male , Humans , Immunity, Cellular , Immunity, Innate , Lymphocyte Activation , Male , Middle Aged , RNA, Viral/blood , Receptors, CCR5/physiology , Risk-Taking , Sequence Deletion , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
AIDS: Development of a safe and effective AIDS vaccine remains a critical issue, particularly in developing nations where HIV infections will account for 90 percent of all new infections by 2000. The AIDS Vaccine Evaluation Group (AVEG) is conducting phase I and II studies of several candidate HIV-1 vaccines. Technical and ethical issues, including significant problems that need to be addressed in vaccine trials, are discussed. The safety of the current candidate vaccines, their immunogenicity, and the continued spread of HIV-1 in spite of educational efforts indicate that clinical trials are warranted. An extensive bibliography of articles related to vaccine development is included.^ieng
Subject(s)
AIDS Vaccines/immunology , Avipoxvirus/immunology , Clinical Trials as Topic , HIV Infections/prevention & control , HIV-1 , Viral Vaccines/immunology , AIDS Vaccines/genetics , AIDS Vaccines/therapeutic use , Animals , Genetic Vectors , HIV Envelope Protein gp120/therapeutic use , HIV Envelope Protein gp160/therapeutic use , HIV Infections/immunology , HIV Infections/transmission , Humans , Immunotherapy/methods , United States , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/genetics , Viral Vaccines/therapeutic useABSTRACT
The corrected sequence of the trkH gene of Escherichia coli predicts that the TrkH protein is a hydrophobic membrane protein of 483 amino acid residues, of which 41% are identical to those of the homologous and functionally analogous TrkG protein. These two proteins form the transmembrane component of the Trk system for the uptake of K+. Each protein alone is sufficient for high-level Trk activity. When Trk is assembled with the TrkG protein, Rb+ and K+ are transported with a Km near or below 1 mM; however, the Vmax for Rb+ is only about 7% of that for K+. When Trk is formed with TrkH, the affinities for both for K+ and Rb+ are somewhat lower, and the Vmax for Rb+ is only 1% of that for K+ transport. The kinetics of transport in strains with wild-type alleles at trkG and at trkH suggest that both products participate in transport.
