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2015 ; 5
(ä): 15438
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Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation:
First report of emergence of B/C recombinants from North India
#MMPMID26494109
Ronsard L
; Raja R
; Panwar V
; Saini S
; Mohankumar K
; Sridharan S
; Padmapriya R
; Chaudhuri S
; Ramachandran VG
; Banerjea AC
Sci Rep
2015[Oct]; 5
(ä): 15438
PMID26494109
show ga
HIV-1 is characterized by high genetic heterogeneity which is a challenge for
developing therapeutics. Therefore, it is necessary to understand the extent of
genetic variations that HIV is undergoing in North India. The objective of this
study was to determine the role of genetic and functional role of Vif on APOBEC3G
degradation. Vif is an accessory protein involved in counteracting APOBEC3/F
proteins. Genetic analysis of Vif variants revealed that Vif C variants were
closely related to South African Vif C whereas Vif B variants and Vif B/C showed
distinct geographic locations. This is the first report to show the emergence of
Vif B/C in our population. The functional domains, motifs and phosphorylation
sites were well conserved. Vif C variants differed in APOBEC3G degradation from
Vif B variants. Vif B/C revealed similar levels of APOBEC3G degradation to Vif C
confirming the presence of genetic determinants in C-terminal region. High
genetic diversity was observed in Vif variants which may cause the emergence of
more complex and divergent strains. These results reveal the genetic determinants
of Vif in mediating APOBEC3G degradation and highlight the genetic information
for the development of anti-viral drugs against HIV. IMPORTANCE: Vif is an
accessory HIV-1 protein which plays significant role in the degradation of human
DNA-editing factor APOBEC3G, thereby impeding the antiretroviral activity of
APOBEC3G. It is known that certain natural polymorphisms in Vif could degrade
APOBEC3G relatively higher rate, suggesting its role in HIV-1 pathogenesis. This
is the first report from North India showcasing genetic variations and novel
polymorphisms in Vif gene. Subtype C is prevalent in India, but for the first
time we observed putative B/C recombinants with a little high ability to degrade
APOBEC3G indicating adaptation and evolving nature of virus in our population.
Indian Vif C variants were able to degrade APOBEC3G well in comparison to Vif B
variants. These genetic changes were most likely selected during adaptation of
HIV to our population. These results elucidate that the genetic determinants of
Vif and highlights the potential targets for therapeutics.
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