Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription

Abstract

Viruses are completely dependent upon cellular machinery to support replication and have therefore developed strategies to co-opt cellular processes to optimize infection and counter host immune defenses. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode a relatively small number of genes. Viruses with limited genetic content often encode multifunctional proteins that function at multiple stages of the viral replication cycle. In this review, we discuss the functions of HIV-1 regulatory (Tat and Rev) and accessory (Vif, Vpr, Vpu, and Nef) proteins. Each of these proteins has a highly conserved primary activity; however, numerous additional activities have been attributed to these viral proteins. We explore the possibility that HIV-1 proteins leverage their multifunctional nature to alter host transcriptional networks to elicit a diverse set of cellular responses. Although these transcriptional effects appear to benefit the virus, it is not yet clear whether they are strongly selected for during viral evolution or are a ripple effect from the primary function. As our detailed knowledge of these viral proteins improves, we will undoubtedly uncover how the multifunctional nature of these HIV-1 regulatory and accessory proteins, and in particular their transcriptional functions, work to drive viral pathogenesis.

Reovirus Nonstructural Protein σNS Acts as an RNA Stability Factor Promoting Viral Genome Replication

“…proteins, called nonstructural proteins, participate in multiple viral replication steps, including translation of viral mRNAs (1), replication of viral genomes (2), construction of sites for particle assembly (3), and inhibition of innate immune responses (4). Due to constraints on viral genome size (5), most nonstructural proteins play multiple roles during infection (6). Consequently, teasing out individual activities of viral nonstructural proteins is challenging.…”

Sensor Sensibility—HIV-1 and the Innate Immune Response

“…Another stage where HIV-1 can interfere with the innate immune response is the signaling event itself that follows recognition of a PAMP. There is increasing evidence that HIV-1 causes global changes in the host transcriptional network to manipulate cellular responses including the innate immune response [108]. Although it is well established that HIV-1 uses its Vpu protein to counteract NF-κB signaling, the impact on the global transcriptome, especially genes related to immune responses, remained unclear [109,110].…”

Tat basic domain: A “Swiss army knife” of HIV‐1 Tat?

“…The HIV‐1 genome is composed of nine genes including Tat (transactivator of transcription) coding for a Tat regulatory protein, which plays a pivotal role in regulation of viral transcription . Depending on the HIV‐1 strain, the length of Tat varies between 86 to 104 aa.…”

“…The HIV-1 genome is composed of nine genes including Tat (transactivator of transcription) coding for a Tat regulatory protein, which plays a pivotal role in regulation of viral transcription. [1][2][3] Depending on the HIV-1 strain, the length of Tat varies between 86 to 104 aa. The Tat gene is composed of two exons: the first exon codes for 72 amino acids; the remaining part of the protein is encoded by the second exon ( Figure 1).…”