Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the modified vaccinia Ankara (MVA) virus, and a replication incompetent adenovirus type 5 (Ad5) vector-expressing the SIV gag protein for their ability to elicit such immune responses in monkeys. The vaccines were tested either as a single modality or in combined modality regimens. Here we show that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. After challenge with a pathogenic HIV-SIV hybrid virus (SHIV), the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the virus infection. The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine.

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The virologic and cellular factors that are involved in transmission of human immunodeficiency virus type 1 (HIV-1) across the female genital tissue are poorly understood. We have recently developed a human cervical tissue-derived organ culture model to study heterosexual transmission of HIV-1 that mimics the in vivo situation. Using this model we investigated the role of phenotypic characteristics of HIV-1 and identified the cell types that are first infected during transmission. Our data indicate that the cell-free R5 HIV-1 was more efficiently transmitted than cell-free X4 HIV-1. Cell-free and cell-associated HIV-1 had comparable transmission efficiency regardless of whether the virus was of R5 or X4 type. We have demonstrated that memory CD4 Heterosexual transmission accounts for the majority of worldwide human immunodeficiency virus type 1 (HIV-1) infections in women (17,20,21). Very little is known about the role of biologic and molecular characteristics of HIV-1 during sexual transmission. Since semen has been shown to contain free infectious HIV-1 and HIV-1-infected cells (19,26,(32)(33)(34)(35), transmission could potentially occur via cell-free and cell-associated HIV-1. Studies on the viral envelope sequence in men during primary infection suggest that virus transmitted during sexual contact was mostly homogeneous and had macrophagetropic and non-syncytium-inducing phenotypes (35, 37). However, recent data of Long et al. (16) indicate that heterogeneous HIV-1 was found in women, whereas homogeneous virus was detected in men soon after sexual contact, indicating that the mechanism of sexual transmission of HIV-1 in women could be different than that in men.There are no in vivo data to indicate the cell types that first become infected in the reproductive tract of women. Although in chronically HIV-1-infected women T cells, macrophages, and Langerhans cells in cervical tissue are infected with HIV-1 (25, 26), analysis of lymph nodes in HIV-infected men during the acute phase of infection indicates that actively virus replication occurs in activated and resting CD4 ϩ T cells (36). A number of studies have demonstrated that productively HIV-1-infected cells in vivo are memory T cells (CD4 ϩ CD45RO ϩ ) that respond to antiretroviral therapy (22,24). There is controversy in the simian immunodeficiency virus (SIV)-rhesus monkey model system about the types of cells that become first infected during sexual transmission. Spira et al. (28) found that cells which initially become infected in the female genital tract are Langerhans cells present in the lamina propria, but the identity of these cells could not be determined by specific immunohistochemical staining on contiguous tissues. Moreover, this study could not determine whether these HIV-1 DNA-containing cells were productively infected. On the other hand, using simultaneous in situ hybridization and immunohistochemical staining, Zhang et al. (36) recently found that CD4 ϩ T (both activated and resting) cells and not dendritic cells were predominantly the...

Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion quantum simulator to observe the signatures of a nonequilibrium driven phase without disorder—the prethermal discrete time crystal. Here, the heating problem is circumvented not by disorder-induced many-body localization, but rather by high-frequency driving, which leads to an expansive time window where nonequilibrium phases can emerge. Floquet prethermalization is thus presented as a general strategy for creating, stabilizing, and studying intrinsically out-of-equilibrium phases of matter.