HIV gp41 and glutathione peroxidases 24 October 2003
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Christopher J Noble,
postdoctoral fellow
Bern Switzerland

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Re: HIV gp41 and glutathione peroxidases

Dear James, The letter in JAIDS you cited is of interest because it provides a possible explanation for the correlation between selenium depletion and HIV infection. The same authors have subsequently published a full article (1)

It is important to note that the sequence similarity between the HIV sequence and mammalian glutathione peroxidases is very weak by "Perth Group" standards.

The sequence alignments are given in figure 1. Out of the ~89 amino acids in the HIV sequence only 28 are present in at least one of the mammalian glutathione peroxidase sequences. Hence there is less than 31% similarity. This does not take into account three major deletions which were necessary to align the sequences.

Nevertheless these researchers have shown that this HIV sequence can potentially code for a selenoprotein that has glutathione peroxidase activity. It performs the same function as mammalian glutathione peroxidases - it catalyses the reduction of hydroperoxides such as hydrogen peroxides.

The key criteria for the conservation of the function of glutathione peroxidases is three key residues containing respectively, selenocysteine, glutamine, and tryptophan at the active site. Substitutions in other parts of the sequence as long as they don't dramatically change the folding of the protein will not affect its activity. This can be seen in the variation in the mammalian glutathione peroxidase sequences.

This example effectively demonstrates the relationship between genetic sequence and protein function.

It should also be noted that these authors also claim that sequences coding for selenoproteins can also be found in other viruses including hepatitis B, Coxsackie virus B3 and MMTV (2).

(1) Lijun Zhao, Arthur G. Cox, Jan A. Ruzicka, Ajita A. Bhat, Weiqing Zhang, and Ethan Will Taylor. Molecular modeling and in vitro activity of an HIV-1-encoded glutathione peroxidase, PNAS 97, 2000, 6356-6361

(2) Taylor EW, Nadimpalli RG, Ramanathan CS, Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res 56, 1997, 63-91.

Competing interests: None declared