Background. N-linked glycosylation is a major mechanism for minimizing virus neutralizing antibody response and is present on the Human Immunodeficiency Virus (HIV) envelope glycoprotein. Although it is known that glycosylation changes can dramatically influence virus recognition by the host antibody, the actual contribution of compartmental differences in N-linked glycosylation patterns remains unclear. Methodology and Principal Findings. We amplified the env gp120 C2-V5 region and analyzed 305 clones derived from plasma and other compartments from 15 HIV-1 patients. Bioinformatics and Bayesian network analyses were used to examine N-linked glycosylation differences between compartments. We found evidence for cellspecific single amino acid changes particular to monocytes, and significant variation was found in the total number of N-linked glycosylation sites between patients. Further, significant differences in the number of glycosylation sites were observed between plasma and cellular compartments. Bayesian network analyses showed an interdependency between N-linked glycosylation sites found in our study, which may have immense functional relevance. Conclusion. Our analyses have identified single cell/compartment-specific amino acid changes and differences in N-linked glycosylation patterns between plasma and diverse blood leukocytes. Bayesian network analyses showed associations inferring alternative glycosylation pathways. We believe that these studies will provide crucial insights into the host immune response and its ability in controlling HIV replication in vivo. These findings could also have relevance in shielding and evasion of HIV-1 from neutralizing antibodies.
Bibliographical noteFunding Information:
The authors are thankful to all the patients for their consent to give samples and their participation. YSH is thankful to USYD for the Australian Post-graduate Award. ABA was supported by Fundação para a Ciência e Tecno-logia (Grant nr SFRH/BD/19334/2004). This work has been presented orally at the International Aids Society (IAS) 2007 conference in Sydney, Australia in the HIV diversity, tropism and compartmentalization session of the basic science track.
ASJC Scopus subject areas
- Infectious Diseases