Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine

Udaykumar Ranga, Raj Shankarappa, Nagadenahalli B. Siddappa, Lakshmi Ramakrishna, Ramalingam Nagendran, Marthandan Mahalingam, Anita Mahadevan, Narayana Jayasuryan, Parthasarathy Satishchandra, Susarla K. Shankar, Vinayaka R. Prasad

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.

Original languageEnglish (US)
Pages (from-to)2586-2590
Number of pages5
JournalJournal of Virology
Volume78
Issue number5
DOIs
StatePublished - Mar 2004

Fingerprint

tat Gene Products
chemokines
Human immunodeficiency virus 1
Chemokines
dementia
HIV-1
monocytes
Dementia
Monocytes
Viruses
viruses
proteins
incidence
mutants
Incidence
site-directed mutagenesis
transcriptional activation
Site-Directed Mutagenesis
serine
Serine

ASJC Scopus subject areas

  • Immunology

Cite this

Ranga, U., Shankarappa, R., Siddappa, N. B., Ramakrishna, L., Nagendran, R., Mahalingam, M., ... Prasad, V. R. (2004). Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine. Journal of Virology, 78(5), 2586-2590. https://doi.org/10.1128/JVI.78.5.2586-2590.2004

Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine. / Ranga, Udaykumar; Shankarappa, Raj; Siddappa, Nagadenahalli B.; Ramakrishna, Lakshmi; Nagendran, Ramalingam; Mahalingam, Marthandan; Mahadevan, Anita; Jayasuryan, Narayana; Satishchandra, Parthasarathy; Shankar, Susarla K.; Prasad, Vinayaka R.

In: Journal of Virology, Vol. 78, No. 5, 03.2004, p. 2586-2590.

Research output: Contribution to journalArticle

Ranga, U, Shankarappa, R, Siddappa, NB, Ramakrishna, L, Nagendran, R, Mahalingam, M, Mahadevan, A, Jayasuryan, N, Satishchandra, P, Shankar, SK & Prasad, VR 2004, 'Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine', Journal of Virology, vol. 78, no. 5, pp. 2586-2590. https://doi.org/10.1128/JVI.78.5.2586-2590.2004
Ranga U, Shankarappa R, Siddappa NB, Ramakrishna L, Nagendran R, Mahalingam M et al. Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine. Journal of Virology. 2004 Mar;78(5):2586-2590. https://doi.org/10.1128/JVI.78.5.2586-2590.2004
Ranga, Udaykumar ; Shankarappa, Raj ; Siddappa, Nagadenahalli B. ; Ramakrishna, Lakshmi ; Nagendran, Ramalingam ; Mahalingam, Marthandan ; Mahadevan, Anita ; Jayasuryan, Narayana ; Satishchandra, Parthasarathy ; Shankar, Susarla K. ; Prasad, Vinayaka R. / Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine. In: Journal of Virology. 2004 ; Vol. 78, No. 5. pp. 2586-2590.
@article{621e1e8185464ad0bc75b27c397170e1,
title = "Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine",
abstract = "Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2{\%} versus 15 to 30{\%}). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99{\%}) conserved in non-subtype C viruses and more than 90{\%} of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.",
author = "Udaykumar Ranga and Raj Shankarappa and Siddappa, {Nagadenahalli B.} and Lakshmi Ramakrishna and Ramalingam Nagendran and Marthandan Mahalingam and Anita Mahadevan and Narayana Jayasuryan and Parthasarathy Satishchandra and Shankar, {Susarla K.} and Prasad, {Vinayaka R.}",
year = "2004",
month = "3",
doi = "10.1128/JVI.78.5.2586-2590.2004",
language = "English (US)",
volume = "78",
pages = "2586--2590",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine

AU - Ranga, Udaykumar

AU - Shankarappa, Raj

AU - Siddappa, Nagadenahalli B.

AU - Ramakrishna, Lakshmi

AU - Nagendran, Ramalingam

AU - Mahalingam, Marthandan

AU - Mahadevan, Anita

AU - Jayasuryan, Narayana

AU - Satishchandra, Parthasarathy

AU - Shankar, Susarla K.

AU - Prasad, Vinayaka R.

PY - 2004/3

Y1 - 2004/3

N2 - Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.

AB - Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.

UR - http://www.scopus.com/inward/record.url?scp=10744233168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744233168&partnerID=8YFLogxK

U2 - 10.1128/JVI.78.5.2586-2590.2004

DO - 10.1128/JVI.78.5.2586-2590.2004

M3 - Article

VL - 78

SP - 2586

EP - 2590

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 5

ER -