Etemad Behzad, Gonzalez Oscar A, White Laura, Laeyendecker Oliver, Kirk Gregory D, Mehta Shruti, Sagar Manish
Boston University School of Medicine, Boston, MA, USA.
Boston University School of Public Health, Boston, MA, USA.
Retrovirology. 2014 Nov 28;11:106. doi: 10.1186/s12977-014-0106-8.
Mucosally 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.
Virus 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.
Similar 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.
黏膜获得性人类免疫缺陷病毒1型（HIV-1）感染由有限数量的变异株引起，这些感染毒株可能具有独特的特性，如对进入阻滞剂的敏感性增加、相对干扰素-α（IFN-α）耐药以及在某些原代细胞中的复制差异。关于通过注射吸毒（IDU）感染的受试者在感染后早期发现的HIV-1包膜变异株的表型特性尚无数据。我们首次比较了估计感染前（HIV RNA+/Ab-）、感染后1年内（早期）和超过2年（慢性期）采样的注射吸毒者中病毒包膜的特征。
与疾病慢性期采样的7名无关个体相比，7名HIV RNA+/Ab-受试者的病毒包膜具有更低的遗传多样性和差异度。与慢性期包膜相比，包含HIV RNA+/Ab-的具有复制能力的重组病毒对CCR5受体抑制剂和IFN-α显著更敏感，并且对融合阻滞剂表现出更高敏感性的统计趋势。与慢性感染包膜相比，早期包膜对CCR5、融合抑制剂和IFN-α也表现出统计趋势或显著更高的敏感性。与慢性包膜病毒相比，HIV RNA+/Ab-病毒在成熟单核细胞衍生树突状细胞-CD4+T细胞共培养物中的复制程度较低，但在具有来自3个不同感染阶段包膜的病毒之间，其他原代细胞中没有显著的复制差异。
与黏膜获得性感染相似，血清转化前注射吸毒者中存在的HIV-1包膜准种与疾病慢性期循环的准种相比具有独特的表型特性。
