Bacteria and viruses pose serious challenges for humans because they evolve continuously. Despite ongoing efforts, antiviral drugs to treat many of the most troubling viruses have not been approved yet. The recent launch of new antimicrobials is generating hope as more and more pathogens around the world become resistant to available drugs. But extra effort is still needed. One of the current strategies for antiviral and antibiotic drug development is the search for host cellular pathways used by many different pathogens. For example, many viruses and bacteria alter lipid synthesis and transport to build their own organelles inside infected cells. The characterization of these interactions will be fundamental to identify new targets for antiviral and antibiotic drug development. This review discusses how viruses and bacteria subvert cell machineries for lipid synthesis and transport and summarises the most promising compounds that interfere with these pathways.
Previous studies have shown that a major block to HIV-1 replication in common marmosets operates at the level of viral entry and that this block can be overcome by adaptation of the virus in tissue-cultured cells. However, our current studies indicate that HIV-1 encounters additional postentry blocks in common marmoset peripheral blood mononuclear cells. Here, we show that the common marmoset APOBEC3G (A3G) and BST2 proteins block HIV-1 in cell cultures. Using a directed-evolution method that takes advantage of the natural ability of HIV-1 to mutate during replication, we have been able to overcome these blocks in tissue-cultured cells. In the adapted viruses, specific changes were observed in gag, vif, env, and nef. The contribution of these changes to virus replication in the presence of the A3G and BST2 restriction factors was studied. We found that certain amino acid changes in Vif and Env that arise during adaptation to marmoset A3G and BST2 allow the virus to replicate in the presence of these restriction factors. The changes in Vif reduce expression levels and encapsidation of marmoset APOBEC3G, while the changes in Env increase viral fitness and discretely favor cell-to-cell transmission of the virus, allowing viral escape from these restriction factors. T he main cause of AIDS is chronic infection by human immunodeficiency virus type 1 (HIV-1). Without treatment, HIV-1 infection results in a progressive depletion of CD4 ϩ T cells that leads to severe immunodeficiency, characterized by opportunistic infections and certain types of cancer that are the leading causes of death in HIV-1-positive patients.The presence of several barriers to HIV-1 replication in cells of many species narrows the viral tropism to humans and chimpanzees. The limited species tropism of HIV-1 is due to two types of host factors: (i) factors that are required for HIV-1 replication but that exhibit species-specific changes that do not allow efficient use by HIV-1 and (ii) dominant-acting factors that block replication in many species. The latter, also known as restriction factors, are part of so-called intrinsic antiviral immunity. Altogether, intracellular restriction factors can act as powerful barriers to viral replication. However, viruses have developed mechanisms that can antagonize restriction factors in an equally successful way. These viral countermeasures are often proteins encoded by accessory genes that are not needed for viral replication in the absence of restriction factors. The main restriction factors that block HIV-1 and other lentivirus infections at different stages of the viral life cycle are TRIM5␣ (1), APOBEC3G (A3G) (2), BST2 (3, 4), SAMHD1 (5,6), and the recently discovered Mx2 (7-9).BST2, also known as tetherin, CD317, or HM1.24, tethers viral particles to the plasma membrane of the cell, blocking their release (3, 4). BST2 is able to block the release of a broad range of enveloped viruses (10, 11). To escape from the action of BST2, viruses have developed a variety of strategies. In HIV-1, the acce...
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