Virus

About: Virus is a research topic. Over the lifetime, 136914 publications have been published within this topic receiving 5209107 citations. The topic is also known as: infectious agent & viruses.

Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection

Abstract: Here, a protein known as MX2 is shown to be a major effector of interferon-α-mediated resistance to HIV-1 infection: susceptibility of the HIV-1 virus to inhibition by MX2 is dictated by the Capsid region of the viral Gag protein, and inhibition occurs at a late post-entry step of infection. Two groups report in this issue of Nature that the human interferon-induced GTP-binding protein MX2 is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) and a number of other lentiviruses. For some years it had been known that the related protein MX1 can inhibit HIV-1 replication in humans, but MX2 was thought to be devoid of antiviral activity. The anti-HIV-1 action of MX2 is much less dependent on GTPase activity than is the broader antiviral activity of MX1, pointing to possible mechanistic differences between them. Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1), these include widely expressed restriction factors1, such as APOBEC3 proteins2, TRIM5-α3, BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN)8,9,10,11,12,13,14. Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like, IFN-induced myxovirus resistance 2 (MX2, also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-α-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested, has equivalent or reduced effects on divergent simian immunodeficiency viruses, and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late post-entry step, with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally, human MX1 (also known as MXA), a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus15,16, does not affect HIV-1, whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.

Mutations in the Precore Region of Hepatitis B Virus DNA in Patients with Fulminant and Severe Hepatitis

Abstract: Background. The presence of the hepatitis B e antigen (HBeAg) in serum is known to be a marker of a high degree of viral infectivity. However, fulminant hepatitis may occur in persons who are negative for HBeAg. A single point mutation has been reported to produce a stop codon in the precore region of hepatitis B virus DNA and prevent the formation of the precore protein required to make HBeAg. To determine whether a precore-mutant virus is causally related to severe liver injury, we analyzed the entire precore region in viral strains isolated from patients with fatal cases and uncomplicated cases of hepatitis B. Methods. Serum was obtained from 9 patients with fatal hepatitis B (5 with fulminant and 4 with severe exacerbations of chronic hepatitis) and 10 patients with acute, self-limited hepatitis B. Serum samples from a sex partner implicated as the source of the virus in one case of fulminant hepatitis were also studied. The 87 nucleotides in the precore region of the hepatitis B virus were amplified ...

Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics

Abstract: Electron mnicroscopic studies of adenovirus preparations hla-ve revealed tlle presence of smnall "virus-like" partieles approximately 22 mn, in diameter in a runumber of hum-an and simiarn adenovirus types.' Some workers have irlterpreted these particles as being adenovirus subunits,4e while others' 1 have indicated that they represent a contaminating virus. Our early studies' suggested that lthe 22-m,u particles were viruses which replicated poorly, if at all, in human cells in the absence of adenovirus replication. Atchison et al.2 also presented evidence that the small particles were infectious, that they were defective, and that they were immunologically distinct from any knowii adenovirus antigen. They tentatively referred to this virus as adeno-associated virus (AAV) and we shall continue to use this name. The purpose of the present report is to describe some of the physical, biological, aind immunological characteristics of the small particles found in various adenovirus preparations with further evidenice that they are defective viruses and not adenovirus subunits.

The HIV 'A' (sor) gene product is essential for virus infectivity.

Abstract: The genome of the human immunodeficiency virus (HIV) contains several open reading frames (ORFs) not present in other viruses. The 'A' gene1, also known as Q2P'3, ORF-14 or sor5, partially overlaps the pol gene; its protein product has a relative molecular mass of 23,000 (Mr 23K) and is present in productively infected cells7–10. The function of this protein is unclear; mutant viruses deleted in 'A' replicate in and kill CD4+ lymphocyte lines8, but the high degree of conservation of the deduced amino-acid sequence in nine different HIV isolates (80%) and the presence of analogous genes in HIV-211 and other lentiviruses suggest that the gene function is an important one. Here we describe a mutant virus deficient in the 'A' gene which produces virion particles normally; however, the particles are & sm;1,000 times less infective than wild type. Transcomplementation experiments partially restore infectivity. The mutant virus spreads efficiently when virus-producing cells are co-cultivated with CD4+ lymphocytes, however, indicating that HIV can spread from cell to cell in a mechanism that does not require the 'A' gene product and probably does not require the production of infective virus particles.