Antibody-dependent Enhancement - in HIV-1 Virus Infection

In HIV-1 Virus Infection

ADE of infection has also been reported in HIV. Like DENV, non-neutralizing level of antibodies have been found to enhance the viral infection through interactions of complement system and receptors. The increase in infection has been reported to be over 350 fold which is comparable to ADE in other viruses like DENV. ADE in HIV can be complement mediated or Fc receptor mediated. Complements in presence of HIV-1 positive sera have been found to enhance the infection of MT-2 T-cell line. The Fc-receptor mediated enhancement was reported when HIV infection was enhanced by sera from HIV-1 positive guinea pig enhanced the infection of peripheral blood mononuclear cells without the presence of any complements. Complement Component receptors CR2, CR3 and CR4 have been found to mediate this Complement –Mediated enhancement of infection. The infection of HIV-1 leads to activation of complements fragments of these complements can assist viruses with infection by facilitating viral interactions with host cells that express complement receptors. The deposition of complement on the virus brings the gp120 protein close to CD4 molecules on the surface of the cells, thus leading to facilitated viral entry. Viruses pre-exposed to non-neutralizing complement system have also been found to enhance infections in interdigitating dendritic cells (iDCs). Opsonized viruses have not only shown enhanced entry but also favorable signalling cascades for HIV replication in iDCs. HIV-1 has also showed enhancement of infection in HT-29 cells when the viruses were pre-opsonized with complements C3 and C9 in seminal fluid. This enhanced rate of infection was almost 2 times greater than infection of HT-29 cells with virus alone. Subramanian et al., reported that almost 72% of serum samples out of 39 HIV positive individuals contained complements that were known to enhance the infection. They also suggested that presence of neutralizing antibody (NA) or antibody-dependent cellular cytotoxicity-mediating antibodies (ADCC) in the serum contains infection enhancing antibodies(IEAs). The balance between the NAs and IEAs changes as the disease progresses. During advanced stages of disease the proportion of IEAs are generally higher than NAs. Increase in viral protein synthesis and RNA production have been reported to occur during the complement mediated enhancement of infection. Cells that are challenged with non neutralizing levels of complements have been found have accelerated release of reverse transcriptase and the viral progeny. The interaction of anti-HIV antibodies with non-neutralizing complement exposed viruses also aid in binding of the virus and the erythrocytes which can lead to a more efficient delivery of viruses to the immune compromised organs.

ADE in HIV has raised questions about the risk of infections to volunteers who have taken subneutalizing levels of vaccine just like any other viruses that exhibit ADE. Gilbert et al., in 2005 reported that there was no ADE of infection when they used rgp120 vaccine in phase 1 and 2 trials. It has been emphasized that much research needs to be done in the field of immunity response to HIV-1, information from these studies can be used to produce a more effective vaccine.