Fear W R, Kesson A M, Naif H, Lynch G W, Cunningham A L
Westmead Institutes of Health Research and Australian National Centre for HIV Virology Research, Westmead Hospital, The University of Sydney, NSW.
J Virol. 1998 Feb;72(2):1334-44. doi: 10.1128/JVI.72.2.1334-1344.1998.
Laboratory-adapted (LA) macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates (e.g., HIV-1(Ba-L)) and low-passage primary (PR) isolates differed markedly in tropism for syngeneic neonatal monocytes, monocyte-derived macrophages (MDMs), and placental macrophages (PMs). Newly adherent neonatal monocytes and cultured PMs were highly refractory to infection with PR HIV-1 isolates yet were permissive for LA M-tropic isolates. Day 4 MDMs were also permissive for LA M-tropic isolates and additionally, were permissive for over half the PR isolates tested. Qualitative differences in PR HIV-1 infection of monocytes/MDMs could not be correlated with CD4 levels alone, and in all three cell types the block to PR HIV-1 strain replication preceded reverse transcription. Neonatal monocyte susceptibility to PR HIV-1 strains correlated with increasing CCR-5 expression during maturation. CCR-5 could not be detected on newly adherent (day 1) neonatal monocytes, in contrast to adult monocytes (H. Naif et al., J. Virol. 72:830-836, 1998), but was readily detectable after 4 to 7 days of culture. However, moderate CCR-5 mRNA levels were present in day 1 neonatal monocytes and remained constant during monocyte maturation. CCR-5 was not detectable on the surface of PMs, yet the receptor was present within permeabilized cells. Notably, two brain-derived PR HIV-1 isolates from a single patient, differing in their V3 loops, were discordant in their abilities to infect neonatal monocytes/MDMs and PMs, yet both isolates could infect newly adherent adult monocytes. Together these data strongly suggest that LA HIV-1 isolates are able to infect neonatal monocytes at earlier stages of maturation and lower-level expression of CCR-5 than PR isolates. The differences between neonatal and adult monocytes in susceptibility to PR isolates may also be related to the level of CCR-5 expression.
实验室适应株（LA）嗜巨噬细胞型（M-tropic）1型人类免疫缺陷病毒（HIV-1）分离株（如HIV-1（Ba-L））和低传代原代（PR）分离株在对同基因新生儿单核细胞、单核细胞衍生巨噬细胞（MDM）和胎盘巨噬细胞（PM）的嗜性上有显著差异。新贴壁的新生儿单核细胞和培养的PM对PR HIV-1分离株的感染具有高度抗性，但对LA M-tropic分离株敏感。培养4天的MDM对LA M-tropic分离株也敏感，此外，对超过一半检测的PR分离株也敏感。单核细胞/MDM对PR HIV-1感染的定性差异不能仅与CD4水平相关，并且在所有三种细胞类型中，PR HIV-1毒株复制的阻断发生在逆转录之前。新生儿单核细胞对PR HIV-1毒株的易感性与成熟过程中CCR-5表达的增加相关。与成人单核细胞（H. Naif等人，《病毒学杂志》72:830 - 836，1998）不同，新贴壁（第1天）的新生儿单核细胞上检测不到CCR-5，但在培养4至7天后很容易检测到。然而，第1天的新生儿单核细胞中存在中等水平的CCR-5 mRNA，并且在单核细胞成熟过程中保持恒定。在PM表面检测不到CCR-5，但在通透化细胞中存在该受体。值得注意的是，来自一名患者的两个脑源PR HIV-1分离株，其V3环不同，在感染新生儿单核细胞/MDM和PM的能力上不一致，但两种分离株都能感染新贴壁的成人单核细胞。这些数据共同强烈表明，与PR分离株相比，LA HIV-1分离株能够在成熟的早期阶段和CCR-5表达水平较低时感染新生儿单核细胞。新生儿和成人单核细胞对PR分离株易感性的差异也可能与CCR-5表达水平有关。
