Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis

Dolcetti, Riccardo, Giagulli, Cinzia, He, Wangxiao, Selleri, Marina, Caccuri, Francesca, Eyzaguirre, Lindsay M., Mazzuca, Pietro, Corbellini, Silvia, Campilongo, Federica, Marsico, Stefania, Giombini, Emanuela, Muraro, Elena, Rozera, Gabriella, De Paoli, Paolo, Carbone, Antonino, Capobianchi, Maria Rosaria, Ippolito, Giuseppe, Fiorentini, Simona, Blattner, William A., Lu, Wuyuan, Gallo, Robert C. and Caruso, Arnaldo (2015) Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis. Proceedings of the National Academy of Sciences of the United States of America, 112 46: 14331-14336. doi:10.1073/pnas.1514748112

Author Dolcetti, Riccardo
Giagulli, Cinzia
He, Wangxiao
Selleri, Marina
Caccuri, Francesca
Eyzaguirre, Lindsay M.
Mazzuca, Pietro
Corbellini, Silvia
Campilongo, Federica
Marsico, Stefania
Giombini, Emanuela
Muraro, Elena
Rozera, Gabriella
De Paoli, Paolo
Carbone, Antonino
Capobianchi, Maria Rosaria
Ippolito, Giuseppe
Fiorentini, Simona
Blattner, William A.
Lu, Wuyuan
Gallo, Robert C.
Caruso, Arnaldo
Title Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
Publication date 2015-11-17
Sub-type Article (original research)
DOI 10.1073/pnas.1514748112
Open Access Status Not Open Access
Volume 112
Issue 46
Start page 14331
End page 14336
Total pages 6
Place of publication Kidlington, Oxford, United Kingdom
Publisher National Academy of Sciences
Collection year 2016
Subject 1000 General
Formatted abstract
Although in decline after successful anti-HIV therapy, B-cell lymphomas are still elevated in HIV-1-seropositive (HIV+) persons, and the mechanisms are obscure. The HIV-1 matrix protein p17 persists in germinal centers long after HIV-1 drug suppression, and some p17 variants (vp17s) activate Akt signaling and promote growth of transformed B cells. Here we show that vp17s derived from four of five non-Hodgkin lymphoma (NHL) tissues from HIV+ subjects display potent B-cell growth-promoting activity. They are characterized by amino acid insertions at position 117-118 (Ala-Ala) or 125-126 (Gly-Asn or Gly-Gln-Ala-Asn-Gln-Asn) among some other mutations throughout the sequence. Identical dominant vp17s are found in both tumor and plasma. Three of seven plasma samples from an independent set of NHL cases manifested multiple Ala insertions at position 117-118, and one with the Ala-Ala profile also promoted B-cell growth and activated Akt signaling. Ultradeep pyrosequencing showed that vp17s with C-terminal insertions are more frequently detected in plasma of HIV+ subjects with than without NHL. Insertion of Ala-Ala at position 117-118 into reference p17 (refp17) was sufficient to confer B-cell growth-promoting activity. In contrast, refp17 bearing the Gly-Asn insertion at position 125-126 did not, suggesting that mutations not restricted to the C terminus can also account for this activity. Biophysical analysis revealed that the Ala-Ala insertion mutant is destabilized compared with refp17, whereas the Gly-Asn form is stabilized. This finding provides an avenue for further exploration of structure function relationships and new treatment strategies in combating HIV-1-related NHL.
Keyword AIDS
B-cell clonogenicity
HIV-1 matrix protein p17
Non-Hodgkin lymphoma
p17 variants
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 16 Feb 2016, 17:13:02 EST by Anthony Yeates on behalf of Learning and Research Services (UQ Library)