Abstract
BackgroundMucosally acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells. There is no data about the phenotypic properties of HIV-1 envelope variants found early after acquisition among subjects infected through injection drug use (IDU). For the first time, we compared the characteristics of virus envelopes among injection drug users sampled prior to seroconversion (HIV RNA+/Ab-), within 1 year (early), and more than 2 years (chronic) after estimated acquisition.ResultsVirus envelopes from 7 HIV RNA+/Ab- subjects possessed lower genetic diversity and divergence compared to 7 unrelated individuals sampled during the chronic phase of disease. Replication competent recombinant viruses incorporating the HIV RNA+/Ab- as compared to the chronic phase envelopes were significantly more sensitive to a CCR5 receptor inhibitor and IFN-α and showed a statistical trend toward greater sensitivity to a fusion blocker. The early as compared to chronic infection envelopes also demonstrated a statistical trend or significantly greater sensitivity to CCR5 and fusion inhibitor and IFN- α. The HIV RNA+/Ab- as compared to chronic envelope viruses replicated to a lower extent in mature monocyte derived dendritic cells – CD4+ T cell co-cultures, but there were no significant replication differences in other primary cells among the viruses with envelopes from the 3 different stages of infection.ConclusionsSimilar to mucosal acquisition, HIV-1 envelope quasispecies present in injection drug users prior to seroconversion have unique phenotypic properties compared to those circulating during the chronic phase of disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-014-0106-8) contains supplementary material, which is available to authorized users.
Highlights
Acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells
Because greater initial viral diversity is associated with faster disease progression [17], it is possible that characteristics of the infecting quasispecies are likely different among injection drug users compared to individuals who acquire the virus through sexual contact
Among the HIV RNA+/Ab- subjects, we chose to examine envelope quasispecies as opposed to the predicted T/F strains because injection drug users have been shown to acquire a greater number of variants [1,2,3]
Summary
Acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells. This implies that chronic stage variants with decreased replication in the presence of IFN-α have a disadvantage during transmission In aggregate, these findings strongly suggest that the transmitted viruses with genotypic and phenotypic characteristics similar to ancestral strains have preferential advantage in establishing a systemic infection in a naïve host. These findings strongly suggest that the transmitted viruses with genotypic and phenotypic characteristics similar to ancestral strains have preferential advantage in establishing a systemic infection in a naïve host It remains unclear if similar active selection occurs among viruses acquired through IDU as observed during sexual acquisition. We compared properties of the envelope quasispecies isolated from injection drug users sampled prior to HIV-1 seroconversion to those present over the first 2 to 3 years after acquisition
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