Callaway D S, Ribeiro R M, Nowak M A
The Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, University of Oxford, UK.
Proc Biol Sci. 1999 Dec 22;266(1437):2523-30. doi: 10.1098/rspb.1999.0955.
One of the phenotypic distinctions between different strains of human immunodeficiency virus type 1 (HIV-1) has to do with the ability to cause target cells to form large multinucleate bodies known as syncytia. There are two phenotypes according to this characterization: syncytium-inducing (SI) and non-syncytium-inducing (NSI). NSI strains are usually present throughout infection, while SI strains are typically seen at the beginning of the infection and near the onset of AIDS. The late emergence of SI strains is referred to as phenotype switching. In this paper we analyse the factors that lead to phenotype switching and contribute to the dynamics of disease progression. We show that a strong immune system selects for NSI strains while a weak immune system favours SI strains. The model explicitly accounts for the fact that CD4+ cells are both targets of HIV infection and crucial for activating immune responses against HIV In such a model, SI strains can emerge after a long and variable period of NSI dominated infection. Furthermore, versions of the model which do not explicitly account for HIV-specific, activated CD4+ cells do not exhibit phenotype switching, emphasizing the critical importance of this pool of cells.
1型人类免疫缺陷病毒（HIV-1）不同毒株之间的表型差异之一，与致使靶细胞形成称为多核体的大型多核体的能力有关。根据这一特征有两种表型：合胞体诱导型（SI）和非合胞体诱导型（NSI）。NSI毒株通常在整个感染过程中都存在，而SI毒株通常在感染初期和艾滋病发病临近时出现。SI毒株的后期出现被称为表型转换。在本文中，我们分析了导致表型转换并促成疾病进展动态的因素。我们表明，强大的免疫系统会选择NSI毒株，而较弱的免疫系统则有利于SI毒株。该模型明确考虑了这样一个事实，即CD4+细胞既是HIV感染的靶标，又对激活针对HIV的免疫反应至关重要。在这样一个模型中，SI毒株可能在NSI主导感染的漫长且可变的时期后出现。此外，未明确考虑HIV特异性活化CD4+细胞的模型版本不会表现出表型转换，这强调了这群细胞的至关重要性。
