Virology as Biosystematics: Towards Understanding the Viral Infection Biology

Large numbers of virus species exist in the realm of nature, and are now classified into distinct sub-groups based on their biochemical and biological characteristics (Knipe et al., 2007). Viruses are unique in their genomic composition, nucleocapsid/ virion morphology, replication strategy, and/or target host. Even though viruses represent the smallest entity encoding a genetic program and are strictly dependent on hosts for their replication, they adapt themselves in a species-specific and dexterous manner to infect or persist in a wide variety of living things. In the course of interaction with hosts, viruses somehow find ecologica

The Fourth Major Restriction Factor Against HIV/SIV

Human and simian immunodeficiency viruses (HIV/SIVs) carry a unique set of accessory proteins that enhance virus replication in an optimized manner. These viral proteins specific to HIV/SIVs are designated Vif, Vpx, Vpr, Vpu, and Nef, and are functional in certain cell types (Malim and Emerman, 2008; Fujita et al., 2010). While viruses of the HIV-1 group do not encode Vpx, the other HIV-2/SIVs are unable to replicate in cells of the myeloid lineage such as monocyte-derived dendritic cells (MDDCs) and macrophages (MDMs) in the absence of Vpx (Fujita et al., 2010). Vpx and its structural close relative Vpr are leas

コウHIV リョウホウ ノ ゲンジョウ

Despite numerous efforts against HIV/AIDS, the number of people infected with HIV has been increasing, especially in Africa and Asia. As the nature of lentivirus, HIV persists,mutates frequently, and slowly causes AIDS in the presence of host defense mechanism. It is difficult, therefore, to repress the replication of viruses of this category. In this brief review,we summarize the current attempts to find therapeutic modalities for attacking HIV. These include chemotherapy (HAART as representative), vaccine, and gene therapy

Coronavirus Diversification

Human coronaviruses (HCoVs) are of zoonotic origins, and seven distinct HCoVs are currently known to infect humans. While the four seasonal HCoVs appear to be mildly pathogenic and circulate among human populations, the other three designated SARS-CoV, MERS-CoV, and SARS-CoV-2 can cause severe diseases in some cases. The newly identified SARS-CoV-2, a causative virus of COVID-19 that can be deadly, is now spreading worldwide much more efficiently than the other two pathogenic viruses. Despite evident differences in these properties, all HCoVs commonly have an exceptionally large genomic RNA with a rather peculiar gene organization and have the potential to readily alter their biological properties. CoVs are characterized by their biological diversifications, high recombination, and efficient adaptive evolution. We are particularly concerned about the high replication and transmission nature of SARS-CoV-2, which may lead to the emergence of more transmissible and/or pathogenic viruses than ever before. Furthermore, novel variant viruses may appear at any time from the CoV pools actively circulating or persistently being maintained in the animal reservoirs, and from the CoVs in infected human individuals. In this review, we describe knowns of the CoVs and then mention their unknowns to clarify the major issues to be addressed. Genome organizations and sequences of numerous CoVs have been determined, and the viruses are presently classified into separate phylogenetic groups. Functional roles in the viral replication cycle in vitro of non-structural and structural proteins are also quite well understood or suggested. In contrast, those in the in vitro and in vivo replication for various accessory proteins encoded by the variable 3' one-third portion of the CoV genome mostly remain to be determined. Importantly, the genomic sequences/structures closely linked to the high CoV recombination are poorly investigated and elucidated. Also, determinants for adaptation and pathogenicity have not been systematically investigated. We summarize here these research situations. Among conceivable projects, we are especially interested in the underlying molecular mechanism by which the observed CoV diversification is generated. Finally, as virologists, we discuss how we handle the present difficulties and propose possible research directions in the medium or long term

Complete Genome Sequences of Human Immunodeficiency Type 1 Viruses Genetically Engineered To Be Tropic for Rhesus Macaques

We have constructed two human immunodeficiency type 1 (HIV-1) derivatives, CXCR4 tropic and CCR5 tropic, that replicate in rhesus macaques. They are genetically engineered to be resistant to macaque restriction factors against HIV-1, including TRIM5α, APOBEC3, and tetherin proteins. The two HIV-1 variants described here are fundamental clones aiming for rhesus infection studies of HIV-1

Structural Dynamics of Retroviral Genome and the Packaging

Retroviruses can cause diseases such as AIDS, leukemia, and tumors, but are also used as vectors for human gene therapy. All retroviruses, except foamy viruses, package two copies of unspliced genomic RNA into their progeny viruses. Understanding the molecular mechanisms of retroviral genome packaging will aid the design of new anti-retroviral drugs targeting the packaging process and improve the efficacy of retroviral vectors. Retroviral genomes have to be specifically recognized by the cognate nucleocapsid domain of the Gag polyprotein from among an excess of cellular and spliced viral mRNA. Extensive virological and structural studies have revealed how retroviral genomic RNA is selectively packaged into the viral particles. The genomic area responsible for the packaging is generally located in the 5′ untranslated region (5′ UTR), and contains dimerization site(s). Recent studies have shown that retroviral genome packaging is modulated by structural changes of RNA at the 5′ UTR accompanied by the dimerization. In this review, we focus on three representative retroviruses, Moloney murine leukemia virus, human immunodeficiency virus type 1 and 2, and describe the molecular mechanism of retroviral genome packaging