Small Intestine CD4 ⁺ T Cells Are Profoundly Depleted during Acute Simian-Human Immunodeficiency Virus Infection, Regardless of Viral Pathogenicity

Abstract

To analyze the relationship between acute virus-induced injury and the subsequent disease phenotype, we compared the virus replication and CD4 ؉ T-cell profiles for monkeys infected with isogenic highly pathogenic (KS661) and moderately pathogenic (#64) simian-human immunodeficiency viruses (SHIVs). Intrarectal infusion of SHIV-KS661 resulted in rapid, systemic, and massive virus replication, while SHIV-#64 replicated more slowly and reached lower titers. Whereas KS661 systemically depleted CD4 ؉ T cells, #64 caused significant CD4 ؉ T-cell depletion only in the small intestine. We conclude that SHIV, regardless of pathogenicity, can cause injury to the small intestine and leads to CD4 ؉ T-cell depletion in infected animals during acute infection.

The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

“…Like ts1, other cytopathic retroviruses, including HIV-1, SIV and FIV, cause damage to the intestines and selective loss of CD4+ cells [6,[21][22][23][24]. At present, there is still much to learn generally about intestinal responses to cytopathic retrovirus infection, but we believe that our work provides information relevant to HIV-1 enteropathy, and that it identifies GVT as a therapeutic agent that can prevent, maintain, or restore gut epithelial and T cell homeostasis in HIV-AIDS.…”

“…2 shows frozen sections of small intestines from 30 dpi uninfected, ts1-only, and ts1-GVT mice, stained with hematoxylin and eosin (H&E) for cytoarchitecture (A), with anti-gp70 to identify infected cells (B), and with anti-CD4 or anti-CD8 to identify cells in the LP of the villi (C). Hyperproliferation of the crypts is a common intestinal manifestation of infection by other retroviruses, including SIV in nonhuman primates, FIV in cats, and HIV-1 infection in humans [21][22][23][24]. The H&E and gp70-stained ts1-GVT intestine images in Fig.…”

“…Studies in this paper were designed to identify specific effects of ts1 infection on the mouse small intestine, whose symptomatology is similar to that induced by HIV-1, the primate retrovirus SIV, and the feline immunodeficiency virus FIV [21][22][23][24]. The intestines are significant in retroviral diseases for another reason.…”

Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6

“…Most highly pathogenic SHIVs predominantly use CXCR4 (X4) as a co-receptor and preferentially infect naive CD4 + T-lymphocytes, which highly express CXCR4 (Mehandru, 2007). Highly pathogenic SHIVs deplete CD4 + T-lymphocytes in peripheral blood with a rapid reduction in a few weeks, which quickly results in AIDS (Sadjadpour et al, 2004;Reimann et al, 2005;Fukazawa et al, 2008). However, HIV-1 initial clinical isolates and SIVs use CCR5 (R5) as a co-receptor.…”

Acute Infection of Chinese Macaques by a CCR5-Tropic SHIV Carrying a Primary HIV-1 Subtype B' Envelope

“…Immunohistochemistry analysis, however, was performed on formalinfixed paraffin-embedded SIs to determine the loss of CD4 + T cells using a mouse anti-human CD4 monoclonal antibody. 22 CD4 + T cells were stained red as shown in Fig. 4.…”