Three Novel Genes of Human T-lymphotropic Virus Type III: Immune Reactivity of Their Products with Sera from Acquired Immune Deficiency Syndrome Patients

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1986 Apr 1

PMID 3008154

Citations 38

Authors

S K Arya

R C Gallo

Affiliations

Soon will be listed here.

Abstract

Human T-lymphotropic virus type III or lymphoadenopathy associated virus (HTLV-III/LAV) is the cause of acquired immune deficiency syndrome (AIDS). In addition to the conventional retroviral genes involved in virus replication, namely, gag, pol, and env genes, DNA sequence analysis of HTLV-III genome predicted two additional open reading frames termed by us short open reading frame (sor) and 3' open reading frame (3' orf). Furthermore, functional analysis revealed another gene with transactivating function, termed tat. We have now structurally identified and functionally characterized these HTLV-III specific genes by way of cDNA cloning. DNA sequence analysis of the clones shows that the tat and 3' orf genes contain three exons and their transcription into functional mRNA involves two splicing events and that the sor gene contains at least two exons. In vitro transcription and translation of the cloned spliced sequences show that the sor, tat, and 3' orf genes code for polypeptides with apparent mobility of 24-25 kDa, 14-15 kDa, and 26-28 kDa, respectively. All three polypeptides are immune reactive and are immunogenic in the natural host. The results demonstrate that the three extra open reading frames of HTLV-III, two of which are unique to HTLV-III, are in fact genes that function in vivo and further allow the identification of three new and previously unrecognized HTLV-III antigens with differential immunogenicity in individuals with acquired immune deficiency syndrome and related disorders.

Citing Articles

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1.

Savoret J, Mesnard J, Gross A, Chazal N Front Microbiol. 2021; 11:625941.

PMID: 33510738 PMC: 7835632. DOI: 10.3389/fmicb.2020.625941.

The activity of Nef on HIV-1 infectivity.

Basmaciogullari S, Pizzato M Front Microbiol. 2014; 5:232.

PMID: 24904546 PMC: 4033043. DOI: 10.3389/fmicb.2014.00232.

Serine- and arginine-rich proteins 55 and 75 (SRp55 and SRp75) induce production of HIV-1 vpr mRNA by inhibiting the 5'-splice site of exon 3.

Tranell A, Fenyo E, Schwartz S J Biol Chem. 2010; 285(41):31537-47.

PMID: 20685659 PMC: 2951228. DOI: 10.1074/jbc.M109.077453.

Prospects for antisense peptide nucleic acid (PNA) therapies for HIV.

Pandey V, Upadhyay A, Chaubey B Expert Opin Biol Ther. 2009; 9(8):975-89.

PMID: 19534584 PMC: 2792880. DOI: 10.1517/14712590903052877.

Antibody against human immunodeficiency virus type 1 (HIV-1) Tat protein may have influenced the progression of AIDS in HIV-1-infected hemophiliac patients.

Re M, Furlini G, Vignoli M, Ramazzotti E, Zauli G, La Placa M Clin Diagn Lab Immunol. 1996; 3(2):230-2.

PMID: 8991642 PMC: 170285. DOI: 10.1128/cdli.3.2.230-232.1996.

References

Sodroski J, Rosen C, Haseltine W . Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984; 225(4660):381-5. DOI: 10.1126/science.6330891. View

Sodroski J, Patarca R, Rosen C, Wong-Staal F, Haseltine W . Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985; 229(4708):74-7. DOI: 10.1126/science.2990041. View

Melton D, Krieg P, Rebagliati M, Maniatis T, Zinn K, Green M . Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984; 12(18):7035-56. PMC: 320141. DOI: 10.1093/nar/12.18.7035. View

Hahn B, Shaw G, Arya S, Popovic M, Gallo R, Wong-Staal F . Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature. 1984; 312(5990):166-9. DOI: 10.1038/312166a0. View

Chou P, Fasman G . Prediction of protein conformation. Biochemistry. 1974; 13(2):222-45. DOI: 10.1021/bi00699a002. View

Maxam A, Gilbert W . Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980; 65(1):499-560. DOI: 10.1016/s0076-6879(80)65059-9. View

Arya S . Sequence complexity of polyadenylated RNA in human breast carcinoma cells. Int J Biochem. 1982; 14(1):19-24. DOI: 10.1016/0020-711x(82)90171-9. View

KYTE J, Doolittle R . A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982; 157(1):105-32. DOI: 10.1016/0022-2836(82)90515-0. View

Barre-Sinoussi F, Chermann J, Rey F, Nugeyre M, Chamaret S, Gruest J . Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599):868-71. DOI: 10.1126/science.6189183. View

10.

Kozak M . Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo. Nature. 1984; 308(5956):241-6. DOI: 10.1038/308241a0. View

11.

Popovic M, Sarngadharan M, Read E, Gallo R . Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984; 224(4648):497-500. DOI: 10.1126/science.6200935. View

12.

Gallo R, Salahuddin S, Popovic M, Shearer G, Kaplan M, Haynes B . Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984; 224(4648):500-3. DOI: 10.1126/science.6200936. View

13.

Sodroski J, Rosen C, Wong-Staal F, Salahuddin S, Popovic M, Arya S . Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985; 227(4683):171-3. DOI: 10.1126/science.2981427. View

14.

Power M, Barr P, Steimer K, Stempien M, Gee W, Renard A . Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985; 227(4686):484-92. DOI: 10.1126/science.2578227. View

15.

Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon M . Nucleotide sequence of the AIDS virus, LAV. Cell. 1985; 40(1):9-17. DOI: 10.1016/0092-8674(85)90303-4. View

16.

Ratner L, Haseltine W, Patarca R, Livak K, Starcich B, Josephs S . Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985; 313(6000):277-84. DOI: 10.1038/313277a0. View

17.

Muesing M, Smith D, Cabradilla C, Benton C, Lasky L, Capon D . Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985; 313(6002):450-8. DOI: 10.1038/313450a0. View

18.

Arya S, Gallo R . Transcriptional modulation of human T-cell growth factor gene by phorbol ester and interleukin 1. Biochemistry. 1984; 23(26):6685-90. DOI: 10.1021/bi00321a062. View

19.

Allan J, Coligan J, Barin F, McLane M, Sodroski J, Rosen C . Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985; 228(4703):1091-4. DOI: 10.1126/science.2986290. View

20.

Barin F, McLane M, Allan J, Lee T, Groopman J, Essex M . Virus envelope protein of HTLV-III represents major target antigen for antibodies in AIDS patients. Science. 1985; 228(4703):1094-6. DOI: 10.1126/science.2986291. View