NDLI: Association between a naturally arising polymorphism within a functional region of HIV-1 Nef and disease progression in chronic HIV-1 infection

Content Provider	Springer Nature Link
Author	Meribe, Stanley C. Hasan, Zafrul Mahiti, Macdonald Mwimanzi, Francis Toyoda, Mako Mori, Masahiko Gatanaga, Hiroyuki Kikuchi, Tadashi Miura, Toshiyuki Kawana Tachikawa, Ai Iwamoto, Aikichi Oka, Shinichi Ue, Takamasa
Copyright Year	2015
Abstract	HIV-1 Nef mediates downregulation of HLA class I (HLA-I) through a number of highly conserved sequence motifs. We investigated the in vivo implication(s) of naturally arising polymorphisms in functional motifs in HIV-1 Nef that are associated with HLA-I downregulation, including the acidic cluster, polyproline, di-arginine and Met-20 regions. Plasma samples from treatment-naive, chronically HIV-1 infected subjects were collected after obtaining informed consent, and viral RNA was extracted and amplified by nested RT-PCR. The resultant nef amplicons were sequenced directly, and subtype-B sequences with an intact open reading frame (n = 406) were included in our analyses. There was over-representation of isoleucine at position 20 (Ile-20) in our dataset when compared to sequences in the Los Alamos sequence database (17.7 vs. 6.9 %, p = 0.0309). The presence of having Ile-20 in Nef was found to be associated with higher median plasma viral load (p = 0.013), independent of associated codons or viral lineage effects, whereas no clinical association was found with polymorphisms in the other functional motifs. Moreover, introduction of a Met-20-to-Ile mutation in a laboratory strain SF2 Nef resulted in a modest, albeit not statistically significant, increase in HLA class I downregulation activity (p = 0.06). Taken together, we have identified a naturally arising polymorphism, Ile-20, within HIV-1 subtype B Nef that is associated with poorer disease outcome.
Starting Page	2033
Ending Page	2041
Page Count	9
File Format	PDF
ISSN	03048608
Journal	Archives of Virology
Volume Number	160
Issue Number	8
e-ISSN	14328798
Language	English
Publisher	Springer Vienna
Publisher Date	2015-06-10
Publisher Place	Vienna
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Virology Medical Microbiology Infectious Diseases
Content Type	Text
Resource Type	Article
Subject	Virology Medicine

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