Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing

The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4+ T cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing integrin 47 was shown to reduce viral transmission, delay disease progression, and induce persistent virus control in macaques challenged with simian immunodeficiency virus (SIV). We show that integrin 47 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated 47 is functionally active as it binds mucosal addressin cell adhesion molecule–1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM-expressing cells, which in turn mediate trans-infection of bystander cells. Functional 47 is present in circulating virions from HIV-infected patients and SIV-infected macaques, with peak levels during the early stages of infection. In vivo homing experiments documented selective and specific uptake of 47+ HIV-1 virions by high endothelial venules in the intestinal mucosa. These results extend the paradigm of tissue homing to a retrovirus and are relevant for the pathogenesis, treatment, and prevention of HIV-1 infection

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer

Immunopathogenic mechanisms of HIV infection.

A complex array of multiphasic and multifactorial immunopathogenic mechanisms are involved in the establishment and progression of human immunodeficiency virus (HIV) disease. After primary infection, acute viremia occurs with wide dissemination of HIV. During this early viremic phase, the virus is trapped within the processes of follicular dendritic cells in the germinal centers of lymphoid tissue. Also, during this phase of primary infection, some patients show major expansions of certain subsets of CD8+ T cells that are identified by the expression of a particular variable region of the beta chain of the T-cell receptor. These expansions are manifestations of responses to HIV that may be important in controlling the progression of HIV infection. In addition, inappropriate immune activation and elevated secretion of certain proinflammatory cytokines occur during HIV infection; these cytokines play a role in the regulation of HIV expression in the tissues. Infection of progenitor cells in bone marrow and the thymus contribute to the lack of regeneration of immunocompetent cells. Dendritic cells are involved in the initiation and propagation of HIV infection in CD4+ T cells. In studies of long-term nonprogressors - persons who have stable CD4+ T-cell counts and no HIV disease progression despite years of HIV infection - preserved lymph node architecture, low viral burden, and viral expression were found