Genetic and functional characterization of HIV-1 Vif on APOBEC3G degradation: First report of emergence of B/C recombinants from North India.
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.


OBJECTIVE
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.
Virology Laboratory, National Institute of Immunology, New Delhi, India.|Department of Microbiology, University College of Medical Sciences &Guru Teg Bahadur Hospital, Delhi, India.
Larance
L
Ronsard
Virology Laboratory, National Institute of Immunology, New Delhi, India.
Rameez
R
Raja
Department of Microbiology, University College of Medical Sciences &Guru Teg Bahadur Hospital, Delhi, India.
Vaishali
V
Panwar
Department of Virology, VP Chest Institute, University of Delhi, Delhi, India.
Sanjesh
S
Saini
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India.
Kumaravel
K
Mohankumar
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India.
Subhashree
S
Sridharan
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.
Ramamoorthy
R
Padmapriya
Department of Human Physiology, University of Calcutta, Kolkata, India.
Suhnrita
S
Chaudhuri
Department of Microbiology, University College of Medical Sciences &Guru Teg Bahadur Hospital, Delhi, India.
Vishnampettai G
VG
Ramachandran
Virology Laboratory, National Institute of Immunology, New Delhi, India.
Akhil C
AC
Banerjea
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D003564:Cytidine Deaminase / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D010802:Phylogeny; D059748:Proteolysis; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase