A sugar molecule on the HIV-1 gp120 envelope protein that is recognized by the host’s broadly neutralizing antibodies is frequently absent early in infection, and later evolves to escape immune pressure, reports a study published online this week in Nature Medicine.
Some of the most potent broadly neutralizing antibodies against HIV-1 recognize a sugar molecule, called a glycan, at a specific position-Asn 332-on the gp120 envelope. Inducing broadly neutralizing antibodies is a desirable goal of many vaccine strategies. Yet Lynn Morris and colleagues show that in two HIV-1 infected individuals who developed these broadly neutralizing antibodies, the virus present early in their infection lacks the glycan at position 332 and is not neutralized by antibodies targeting this glycan. However, within the first six months of infection in both individuals, the virus acquired the glycan at position 332, presumably to escape recognition by other circulating antibodies. By two years of infection, the glycan at Asn332 disappeared, again the authors conclude, probably due to escape from later-developing glycan-specific broadly neutralizing antibodies.
The authors further found that at a population level, HIV-1 subtype C viruses present during acute infection more frequently lacked the glycan, compared with viruses present during chronic infection, which predominantly contained the glycan at position 332. The authors’ findings chronicle the evolution of HIV-1 in response to antibody-mediated immune pressure and suggest that targeting this glycan might not be sufficient to neutralize founder viruses that initiate HIV-1 infection.